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Conventional bedside tests of visuospatial function such as the Clock Drawing (CDT) and Intersecting Pentagons (IPT) lack consistency in delivery and interpretation. We compared performance on a novel test of visuospatial ability - the LSD - with the IPT, CDT and MMSE in 180 acute elderly medical inpatients [mean age 79.7±7.1 (range 62-96); 91 females (50.6%)]. 124 (69%) scored ≤23 on the MMSE; 60 with mild (score 18-23) and 64 with severe (score ≤17) impairment. 78 (43%) scored ≥6 on the CDT, while for the IPT, 87 (47%) scored ≥4. The CDT and IPT agreed on the classification of 138 patients (77%) with modest-strong agreement with the MMSE categories. Correlation between the LSD and visuospatial tests was high. A four-item version of the LSD incorporating items 1,10,12,15 had high correlation with the LSD-15 and strong association with MMSE categories. The LSD-4 provides a brief and easily interpreted bedside test of visuospatial function that has high coverage of elderly patients with neurocognitive impairment, good agreement with conventional tests of visuospatial ability and favourable ability to identify significant cognitive impairment. [181 words].

Pacific Earthquake Engineering Research (PEER) Center [00006493]; Longwell's Family Foundation; LSU Council on Research; Louisiana Board of Regents (LA BoR) through the Louisiana Board of Regents Research and Development [LESQSF(2010-13)-RD-A-01]; National Science Foundation [DMS-0915220]; Fundamental Research Funds for the Central Universities of China [2010111075]

Objective. Certolizumab pegol (CZP) is known to be effective as monotherapy at a dosage of 400 mg every 4 weeks in patients with active RA who have failed DMARDs. The aim of this study was to investigate every 4-week CZP in addition to continued MTX therapy in patients with an inadequate response to MTX alone. Methods. Patients with active RA with inadequate response to MTX, on background MTX, were randomized to double-blind treatment with CZP 400 mg or placebo every 4 weeks for 24 weeks (NCT00544154). The primary efficacy end-point was the ACR 20% improvement criteria (ACR20) response rate at Week 24. Other end-points included ACR50 and ACR70 response rates, ACR core components, 28-joint DAS (ESR) with three variables (DAS28-3) and health-related quality-of-life outcomes in addition to safety. Results. Of 247 randomized patients, 126 received CZP and 121 received placebo, in addition to MTX. ACR20 response rates were 45.9 vs 22.9%, respectively [P < 0.001 analysed by the Cochran MantelHaenszel (CMH) method], with improvements being apparent from Week 1. Statistically significant improvements over placebo were seen with CZP for ACR50, ACR core components, DAS28-3 and physical functioning. Rates of treatment-related adverse events were similar between groups (25.0 vs 27.7%), and there were no deaths or serious opportunistic infections. Conclusion. CZP 400 mg every 4 weeks plus MTX demonstrated a favourable riskbenefit profile with rapid onset of action in RA patients with an inadequate response to an earlier MTX therapy.

Object composition offers significant advantages over class inheritance to develop a flexible software architecture for finite-element analysis. Using this approach, separate classes encapsulate fu...

A framework for simulating the material and geometric nonlinear response of frame members is developed from the equations of beam mechanics. The implementation of a beam-column finite element is reduced to the state determination procedure for a basic system that displaces and rotates with the element. An abstraction for geometric nonlinearity represents the kinematic and equilibrium transformations between the basic and global reference systems, while an abstraction for force-deformation response represents material nonlinearity for the basic system. Separate objects encapsulate material stress-strain behavior and cross-sectional integration in order to increase the modeling flexibility for computing the response of fiber-discretized cross sections. Multiple forms of distributed plasticity in beam-column elements are incorporated in the framework through objects that encapsulate one-dimensional quadrature rules. Software design patterns are utilized to create complex beam-column simulation models by composition of basic building blocks. The modeling flexibility of the software design is demonstrated through the simulation of a reinforced concrete column.

Objective. To evaluate the effectiveness and safety of adalimumab in patients with rheumatoid arthritis (RA) who previously discontinued tumour necrosis factor (TNF) antagonists for any reason in clinical practice. Methods. ReAct (Research in Active Rheumatoid Arthritis) was a large, open-label trial that enrolled adults with active RA who had previously been treated with traditional disease-modifying anti-rheumatic drugs or biological response modifiers. Patients selfadministered adalimumab 40 mg subcutaneously every other week for 12 weeks and were allowed to enter an optional long-term extension phase. Measures of adalimumab effectiveness included American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) response criteria, Disease Activity Score 28 (DAS28) and the Health Assessment Questionnaire Disability Index (HAQ DI). Results. Of 6610 patients, 899 had a history of etanercept and/or infliximab therapy; these patients experienced substantial clinical benefit from adalimumab treatment. At week 12, 60% of patients had an ACR20 and 33% had an ACR50 response; 76% had a moderate and 23% had a good EULAR response. In addition, 12% achieved a DAS28 < 2.6, indicating clinical remission, and 13% achieved a HAQ DI score < 0.5. The allergic adverse event rate, regardless of relationship to adalimumab, was 6.5/100-patient-years (PYs) in previously TNF antagonist-exposed patients and 4.3/100-PYs in TNF antagonist naive patients. A multiple regression analysis indicated no statistically significantly increased risk of serious infections in patients who received prior TNF antagonists compared with TNF antagonist naive patients. Conclusion. In typical clinical practice, adalimumab was effective and well-tolerated in patients with RA previously treated with etanercept and/or infliximab.

Objective Although common treatments for osteoarthritis (OA) pain, such as nonsteroidal antiinflammatory drugs (NSAIDs), simple analgesics, and weak opioids, provide relief in some cases, they fail to control pain or are poorly tolerated in many cases. Strong opioids have been used to successfully treat several types of noncancer pain but have rarely been tested in controlled studies. Therefore, we tested the effects of transdermal fentanyl (TDF) in patients with moderate-to-severe OA pain, in a placebo-controlled study. Methods The cohort comprised patients with radiologically confirmed OA of the hip or knee (meeting the American College of Rheumatology criteria) requiring joint replacement and with moderate-to-severe pain that had been inadequately controlled by weak opioids. The patients were randomized to receive TDF or placebo for 6 weeks after a 1-week pretreatment run-in phase. During study treatment, previously prescribed NSAIDs and simple analgesics were continued, but weak opioids were discontinued. All patients had access to paracetamol and metoclopramide. Pain was recorded on a visual analog scale (VAS), and function was assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Results Data were available for 399 patients (202 receiving TDF, 197 receiving placebo), of whom 199 (50%) completed the study. TDF provided significantly better pain relief than placebo, as demonstrated by the primary outcome measure (area under the curve for VAS scores −20 in the TDF group versus −14.6 in the placebo group; P = 0.007). TDF was also associated with significantly better overall WOMAC scores and pain scores. The most common adverse events were nausea, vomiting, and somnolence, and these occurred more often in the TDF group. Conclusion TDF can reduce pain and improve function in patients with knee or hip OA.

Objective To compare the efficacy of the cyclooxygenase 2 (COX-2)–specific inhibitors celecoxib and rofecoxib in treating the signs and symptoms of osteoarthritis (OA). Methods In this randomized, placebo-controlled, double-blind, multicenter study, 475 patients with OA of the knee received either celecoxib 200 mg/day (n = 189), rofecoxib 25 mg/day (n = 190), or placebo (n = 96) for 6 weeks. Arthritis assessments were performed at baseline, week 3, and week 6 (or at the time of early termination). Results In primary measures of efficacy (OA pain score on a 100-mm visual analog scale [VAS] and total domain score on the Western Ontario and McMaster Universities Osteoarthritis Index), celecoxib 200 mg/day and rofecoxib 25 mg/day demonstrated similar efficacy. At week 6, celecoxib was associated with a 34-mm mean improvement on the VAS for OA pain, compared with 31.6 mm for rofecoxib and 21.2 mm for placebo. The difference between celecoxib and rofecoxib was −2.5 mm, with an upper limit of the 95% confidence interval of 2.7 mm and within the prespecified definition of noninferiority. Secondary measures of efficacy showed similar results. All differences in primary and secondary measures of efficacy between the 2 active treatments and placebo were statistically significant (P < 0.02), whereas all of the comparisons of efficacy between celecoxib and rofecoxib met the predefined criteria for noninferiority. All treatments were well tolerated throughout the study, with similar proportions of patients withdrawing due to adverse events. Conclusion Celecoxib 200 mg/day and rofecoxib 25 mg/day are equally efficacious in treating the signs and symptoms of OA.

Voltage-dependent activity around the resting potential is determinant in neuronal physiology and participates in the definition of the firing pattern. Low-voltage-activated T-type Ca2 + channels directly affect the membrane potential and control a number of secondary Ca2 + -dependent permeabilities. We have studied the ability of the cloned T-type channels (alpha1G,H,I) to carry Ca2 + currents in response to mock action potentials. The relationship between the spike duration and the current amplitude is specific for each of the T-type channels, reflecting their individual kinetic properties. Typically the charge transfer increases with spike broadening, but the total Ca2 + entry saturates at different spike durations according to the channel type: 4 ms for alpha1G; 7 ms for alpha1H; and > 10 ms for alpha1I channels. During bursts, currents are inhibited and/or transiently potentiated according to the alpha1 channel type, with larger effects at higher frequency. The inhibition may be induced by voltage-independent transitions toward inactivated states and/or channel inactivation through intermediate closed states. The potentiation is explained by an acceleration in the channel activation kinetics. Relatively fast inactivation and slow recovery limit the ability of alpha1G and alpha1H channels to respond to high frequency stimulation ( > 20 Hz). In contrast, the slow inactivation of alpha1I subunits allows these channels to continue participating in high frequency bursts (100 Hz). The biophysical properties of alpha1G, H and I channels will therefore dramatically modulate the effect of neuronal activities on Ca2 + signalling.

This paper attempts to predict the future of records management software and GMB‘s RecFind‐Corporate product. It looks at a four‐year period through until the year 2003. It answers questions both about the relevance of records management software as a discreet application and about the functionality required by the user community. The raw data on feature‐utilisation used for the graphs within this paper are based upon feedback from a selection of GMB’s 80,000 plus RecFind users around the world. The feedback was obtained via both surveys and direct contact, mostly from direct contact.

Background Non restorative sleep (NRS) is a characteristic symptom of fibromyalgia (FM). A number of studies have reported abnormalities of sleep architecture on polysomnography (PSG) including alpha wave intrusion (AWI) during delta wave sleep (DWS). However, AWI in DWS has also been reported in other conditions including depression or in chronic fatigue. We have compared FM patients with patients who had sleep disturbance from osteoarthritis (OA) and a group of normal healthy control subjects (NHC) to determine if there are specific abnormalities of sleep architecture in FM related to clinical parameters. Methods We studied 19 newly diagnosed FM patients (mean age 41yrs, range 19–58yrs), 17 with OA (mean age 46yrs, range 19–63yrs) with localized pain and sleep disturbance, and ten NHC (mean age 38yrs, range 23–61yrs). All participants were female. The diagnosis was confirmed by a consultant rheumatologist. None were being treated for anxiety or depression or had taken antidepressant, psychoactive or sedative drugs for at least 2 weeks prior to analysis. All completed pain score (VAS), Brief Pain Inventory (BPI), Fatigue Severity Scale (FSS), Epworth Sleepiness Scale (EPS), Pittsburgh Sleep Quality Index (PSQI), Centre for Epidemiologic Studies Depression Scale (CESD), State and Trait Anxiety Scale (STAS), Multidimensional Scales of Health Locus of Control and Perceived Social Support (HLC), and 2 weeks actigraphy and 2 consecutive nights of polysomnography (PSG) at home, scored by a trained sleep researcher. Each frequency band was decomposed and power averaged using spectral analysis. Results Sleep efficiency was significantly worse in FM and OA (p=0.025). Sleep stage transitions (SST) were significantly increased in FM and OA (p=0.019) with a marked increase in SST per hour (p=0.002) compared with NHC with no significant difference between FM and OA. Alpha waves were increased during stage 3 sleep (DWS) in both FM and OA compared with NHC but also with no difference between FM and OA. There was a numerical increase in spindle frequency during non REM sleep compared with NHC, more in FM than OA but with wide variation (1.12 ± 0.8; 0.98 ± 0.39; 0.61 ± 0.27 mpl). Pain scores in FM and OA groups were significantly different to NHC; mean difference in BPI of 6.07 and 4.83 respectively (p Conclusions Patients with FM had a similar duration of sleep to this group of OA patients but had a significant difference in subjective sleep quality, with significantly increased fatigue and sleepiness. They also had more anxiety, depression and neuroticism. AWI in DWS in FM is not specific and is similar in disturbed sleep from OA, but increased spindle frequency may be a feature of FM. We hypothesise that psychological factors in FM are linked to both sleep quality and fatigue and NRS may result from an increased rate of SST with frequent fluctuation between light and deep sleep. Disclosure of Interest None declared

Background The duration of steroid treatment in polymyalgia rheumatic (PMR) is variable. Some patients do not have raised inflammatory markers and anecdotal evidence suggests they may need a shorter duration of treatment. In order to evaluate parameters that may predict the duration of steroid treatment we have undertaken a retrospective analysis of patients on our database with a diagnosis of PMR. Methods We evaluated patients who presented with new onset PMR to the Trafford Rheumatology Unit between 2005 and 2010. Following a 14 day therapeutic trial of prednisolone 20mg od and a diagnosis of PMR confirmed by a consultant rheumatologist, all patients received a standard reducing regime of prednisolone, reducing every 2 weeks to initial maintenance of alternate day 10mg/5mg after 2 months (if possible). Doses were increased for recurrence of symptoms. After 6 months the dose was reduced to 5mg od if they had not required a dose increase and tailed off once asymptomatic on 5mg od for 6 months. All patients were followed for 10 years or until drug free remission. The electronic records were reviewed for demographic data, blood count, inflammatory markers, liver enzymes, immunology, and duration of treatment prior to drug free remission. Results 96 patients were evaluated. 15 were excluded from analysis if they had incomplete documentation or because of a positive rheumatoid factor, other immunology or revised diagnosis. The mean age was 68yrs; range 53–90yrs. Female to male ratio was 2.8:1. The median duration of symptoms prior to presentation was 4.5 months (1–36 months). At diagnosis 14% of patients were anaemic, mean CRP was 35mg/l, mean ESR was 45mm/hr and 26% had normal inflammatory markers. Only 1% of patients had raised liver enzymes. 44% were able to reduce to 5mg prednisolone after 6 months and a further 6% after 9 months. The mean duration of steroid treatment for all patients was 30 months (13–108 months). For patients with a normal ESR and CRP at diagnosis, the mean duration of steroids was 22 months compared with 32 months with raised ESR and 35 months with raised CRP. 10% relapsed after steroid withdrawal. 2 patients remained on long term steroids. Conclusions Approximately 25% of patients with PMR do not have raised inflammatory markers at diagnosis and have shorter total duration of steroids (mean 22 months). Almost half can reduce prednisolone to 5mg after 6 months. The average duration of steroids prior to drug free remission is almost 3 yrs in patients with raised inflammatory markers at diagnosis. 10% relapse after gradual steroid withdrawal. Disclosure of Interest None declared

The Standards, Audit and Guidelines Working Group (SAGWG) of the British Society for Rheumatology (BSR) have recently updated the guidelines on eligibility for anti-TNF drugs in RA [1] and have updated the anti-TNF safety and efficacy guidelines [2] for general use of the rheumatology community. The National Institute for Heath and Clinical Excellence (NICE) in the UK, which is the is an independent organization responsible for providing national guidance in the UK on promoting good health and preventing and treating ill health, has published a technology appraisal guidance [3] for use of rituximab in RA in 2007. Furthermore, a consensus statement from EULAR [4] was also published in 2007. Therefore, it was felt appropriate to undertake a review of the currently available data as new evidence was available. The group did not wish to duplicate the guidance in those documents, but wished to review the more recent evidence and supplement what is already known.

Inhibitors of TNF-a represent important treatment advances for a number of inflammatory conditions, including RA. TNF-a inhibitors offer a targeted strategy that contrasts with the non-specific immunosuppressive agents traditionally used to treat most forms of systemic inflammation. Information on who benefits from these agents and on their adverse effects continues to be collected through clinical studies, case series and reports and through national registries. In 2001 and 2005, the British Society for Rheumatology (BSR) established and updated guidelines for the use of anti-TNF drugs in RA [1, 2]. These guidelines have indicated which adult patients with RA should be eligible for treatment with anti-TNF therapies, precautions that need to be taken in their use and action that should be taken in the event of adverse effects. The previous guidelines applied to the then-available anti-TNF therapies {etanercept and infliximab in 2001 [1], and etanercept, infliximab and adalimumab (first-generation anti-TNF agents) in 2005 [2]}. Due to the large volume of information now available on these agents the BSR has, in 2010, produced separate guidelines on eligibility for anti-TNF treatment in RA (in press) These current guidelines cover the safety aspects of anti-TNF treatment in RA and apply to the first-generation products but also to the newly licensed second-generation anti-TNF drugs, certolizumab pegol and golimumab. There are relatively little safety data specifically for these second-generation agents but there are no data thus far to suggest that their side-effect profile would differ significantly from the first-generation agents. This is a rapidly changing field with new data emerging each month, so it is vital that clinicians keep up to date with this area of practice. These guidelines have Rheumatology Department, Royal Derby Hospital, Derby, Rheumatology Unit, Queen Alexandra Hospital, Portsmouth, Rheumatology Department, Nuffield Orthopaedic Centre, Oxford, Rheumatology Department, Poole Hospital, Poole, ARC Epidemiology Unit, University of Manchester, Manchester, Rheumatology Department, St George’s Healthcare, London, Rheumatology Department, Royal Lancaster Infirmary, Lancaster, Rheumatology Department, St Helens Hospital, St Helens, National Rheumatoid Arthritis Society, Maidenhead, Rheumatology Department, Addenbrooke’s Hospital, Cambridge, Rheumatology Department, Trafford General Hospital, Manchester, Rheumatology Unit, Worthing and Southlands NHS Trust, Worthing and Rheumatology Department, Robert Jones and Agnes Hunt Orthopaedic Hospital, Oswestry, UK.

Chris Deighton1, Kimme Hyrich2, Tina Ding1, Jo Ledingham3, Mark Lunt2, Raashid Luqmani4, Patrick Kiely5, Marwan Bukhari6, Rikki Abernethy7, Andrew Ostor8, Ailsa Bosworth9, Kate Gadsby1, Frank McKenna10, Diana Finney11 and Josh Dixey12, on behalf of BSR Clinical Affairs Committee & Standards, Audit and Guidelines Working Group and the BHPR 1Rheumatology Department, Royal Derby Hospital, Derby; 2ARC Epidemiology Unit, University of Manchester, Manchester; 3Rheumatology Unit, Queen Alexandra Hospital, Portsmouth; 4Rheumatology Department, Nuffi eld Orthopaedic Centre, Oxford; 5Rheumatology Department, St George’s Healthcare, London; 6Rheumatology Department, Royal Lancaster Infi rmary, Lancaster; 7Rheumatology Department, St Helens Hospital, St Helens; 8Rheumatology Department, Addenbrooke’s Hospital, Cambridge; 9National Rheumatoid Arthritis Society, Maidenhead; 10Department of Rheumatology, Trafford General Hospital, Manchester; 11Rheumatology Unit, Worthing and Southlands NHS Trust, Worthing; 12Department of Rheumatology, Robert Jones and Agnes Hunt Orthopaedic Hospital, Oswestry, UK

COX-2 specific inhibitors have demonstrated significant safety advantages and comparable efficacy in osteoarthritis (OA) compared with conventional nonsteroidal anti-inflammatory drugs (NSAIDs), but no direct comparative trials between COX-2 specific inhibitors have been published. In this double-blind, placebo-controlled, parallel group, multicenter study, 182 patients (or =40 years old) with OA of the knee were randomly assigned to treatment with celecoxib 200 mg q.d. (n = 63), rofecoxib 25 mg q.d. (n = 59), or placebo (n = 60) for 6 weeks. Arthritis assessments were performed at baseline and Weeks 3 and 6, or at early termination. At Week 6, celecoxib and rofecoxib treatment resulted in similar mean changes from baseline (p0.55) in arthritis pain visual analogue scale, patient's global assessment, and total score for WOMAC; all changes were superior to placebo (p0.05). In the patient's global assessment of arthritis pain at Week 6, 79% of celecoxib-treated and 78% of rofecoxib-treated patients improved byor =1 grade, compared with 50% of placebo patients (celecoxib, p = 0.025; rofecoxib, p = 0.020). Adverse event incidences were similar among the active comparators; however, celecoxib-treated patients had significantly fewer adverse gastrointestinal symptoms compared with rofecoxib-treated patients, which suggests that celecoxib may have a better gastrointestinal tolerability profile than rofecoxib at these doses. Adverse events that prompted withdrawal occurred in fewer than 7% of patients, and the overall incidences were similar between the active agents. Once-daily doses of celecoxib 200 mg and rofecoxib 25 mg offer comparable efficacy and are an effective alternative to conventional NSAIDs in the management of OA.

Sclerosing mesenteritis is a rare condition that is characterized by fibrosis affecting mainly small-bowel mesentery, which in extensive cases may mimic advanced intra-abdominal malignancy. Establishing the diagnosis in such cases is a clinical and histopathologic challenge. We report the successful management of a case of extensive sclerosing mesenteritis with occult ileal perforation, which was possibly the triggering cause. Severe complications occurred as a result of both the disease itself and its surgical treatment. Despite the complex course and life-threatening complications, a good prognosis can be expected. Although occasional recovery has been attributed to spontaneous regression and response to immunosuppressive therapy, a search for, and full eradication of, possible triggering focus is of paramount importance.

A 79 year old woman, whose medical history included diabetes and recurrent urinary tract infections, presented with left sided hip pain. A plain …

Background Compared to other clinical groups with chronic pain, people with fibromyalgia syndrome (FMS) report higher levels of fatigue. It is not known whether this is driven by pain, psychological mechanisms or sleep disturbance. This study compared fatigue outcomes in patients with FMS and osteoarthritis (OA). The patients were part of a larger clinical assessment of psychosocial and polysomnographic variables. Objectives To determine the factors causing fatigue in FMS Methods 20 recently diagnosed FMS patients (all females; M=40.45, SD=11.21 range 19-58yrs) and 15 patients with OA (all females; M=44.60, SD=11.01 range 19-60yrs) exhibiting localized joint pain and sleep disturbance and were recruited from a single rheumatology unit at Trafford General Hospital, UK. All patients with FM fulfilled the 2010 ACR criteria for the diagnosis, confirmed by an experienced rheumatologist. All patients with OA had radiographic abnormality requiring surgical intervention. All participants completed self-reported sleep scores (Pittsburgh Sleep Quality Index), pain (VAS), fatigue (Fatigue Severity Scale), depression and anxiety measures (Hospital Anxiety and Depression score). All patients had 2 weeks actigraphic assessment of sleep. Multiple regression analysis was conducted with fatigue as the dependent variable and sleep, pain, depression and anxiety measures as predictors. Correlation with fatigue was evaluated compared with actigraphic parameters. Results The mean fatigue score in FMS was 51±8.40 and 38.27±10.92 in OA. The regression model was significant overall, F(21,10)=4.63, p=0.002, r 2 =0.54. After controlling for sleep quality, pain severity, pain interference, depression and anxiety, group membership was the only significant predictor of fatigue, B=-7.55, t=-2.40, p=0.026. Fatigue in FMS was correlated with duration of waking after sleep onset and number of awakenings on actigraphy (p=0.034). Conclusions This data shows that differences in fatigue noted in these two clinical groups are not solely driven by psychological factors. Other factors related to sleep structure may play a larger role in driving these differences. The number and duration of awakenings during sleep contribute to fatigue in FMS but not in OA. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.6010

There is little consensus in the management of fibromyalgia (FM) leading to significant disparity of treatment protocols in different rheumatology and pain clinics. The problem in developing effective management guidelines has been the paucity of appropriate clinical trial data. Some management programmes focus on physical and cognitive therapy but may neglect drug therapy. In order to develop a logical approach it is necessary to consider both the symptoms and pathophysiology of the disease. Most patients with FM have a recognisable phenotype and may be described as psychologically vulnerable. A number of studies have documented that a history of physical or sexual abuse is more common in FM compared to control populations. Depression, ill health and catastrophising behaviour are often present prior to the onset of FM and persistent symptoms often lead to treatment focussed on behavioural therapy. However, this is only one facet of the illness. Evidence for augmented processing of pain and impaired endogenous pain inhibition in FM may help to explain the mechanism of altered pain perception. Controlled functional magnetic resonance imaging (fMRI) studies have demonstrated that patients with FM exhibit higher sensitivity to pain provocation – a reduced stimulus in FM causes the same activity in the brain compared with a stronger painful stimulus in controls. This may be explained by a lack of response to painful stimuli in the rostral anterior cingulate cortex (rACC) – part of the descending pain regulating system. More recent studies have suggested that this may result from reduced connectivity of the rACC with the amygdala, hippocampus, and brainstem in FM patients compared with healthy controls. Although the cause of these abnormalities is unclear, we can hypothesise that disordered sleep architecture may explain the development of abnormal pain mechanisms in vulnerable patients. We know from volunteer studies that pain threshold is significantly reduced following deprivation of slow wave sleep (SWS), and fMRI studies of sleep have found reduced activity in a number of structures relating to pain pathways including the ACC, especially during SWS. Longitudinal population studies have found sleep disturbance to be a major risk factor for developing FM, and polysomnographic studies support the hypothesis that fibromyalgia may be a primary disorder of sleep. Altered sleep architecture is found in most studies. There is evidence that fatigue in fibromyalgia is causally related to sleep disturbance. Following restoration of deep sleep with sodium oxybate treatment in FM, fatigue improves in addition to significant improvement in pain and other symptoms. Current data therefore supports the hypothesis that both fatigue and chronic widespread pain in FM result from abnormalities in sleep architecture in patients with psychological vulnerability, leading to dysfunction in the descending pain regulating system. These data suggest that management of FM should be multifaceted. In addition to physical, behavioural and other psychological therapies, treatment programmes must include active management of sleep pathology. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.6286

This report investigates the question: can seismic demands on steel moment-frame buildings due to Maximum Considered Earthquake (MCER) design-level ground motions [2% probability of exceedance (PE) in 50 years] be estimated satisfactorily using linear viscous damping models or is a nonlinear model, such as capped damping, necessary? This investigation employs two models of a 20-story steel moment-frame building: a simple model and an enhanced model with several complex features. Considered are two linear viscous damping models: Rayleigh damping and constant modal damping; and one nonlinear model where damping forces are not allowed to exceed a pre-defined bound. Presented are seismic demands on the building due to two sets of ground motions (GMs): MCER design-level GMs (2% PE in 50 years) and rarer excitations (1% PE in 50 years); and even more intense GMs. Based on these results, we do not recommend Rayleigh damping for use in nonlinear response history analysis (RHA) of buildings. Recommended instead is constant modal damping, which also is available in commercial computer codes. Although satisfactory for estimating seismic demands for MCER design-level motions and even more intense GMs, this damping model may not be appropriate for extreme motions that deform the structure close to collapse. Updated October 5, 2020: Revision 1 was issued September 2020, with the following information provided by the authors. Two sections—Introduction and Conclusions—of the report, first issued in June 2020, were expanded in September 2020. These revisions were prompted by comments on a paper submitted to the journal Earthquake Engineering and Structural Dynamics. These comments came from two anonymous reviewers and Michael Constantinou, the editor. The conclusions now emphasize several results of interest to the profession: First, linear viscous damping models are adequate for estimating seismic demands on buildings—designed to satisfy current story drift and plastic rotation limits—due to MCER design-level ground motions (GMs). Second, between the two linear damping models—Rayleigh damping and constant modal damping—the latter is preferable for nonlinear RHA of buildings because it leads to modestly larger demands. This is a prudent choice in the absence of a benchmark or “exact” result. Third, we do not recommend the Rayleigh damping model in nonlinear RHA of buildings because it leads to smaller demands and, hence, could lead to the conclusion that design or evaluation criteria have been satisfied, when other linear damping models lead to the opposite conclusion. Furthermore, various problems and deficiencies have been identified with Rayleigh damping depending on how the yielding elements in the building are modeled. Fourth, if the goal is to arrive at conclusions valid for professional practice, research investigations on modeling damping in nonlinear RHA of buildings should be based on realistic, state-of-the-practice models of buildings subjected to an ensemble of GMs that correspond to the MCER and have been selected by modern methods. In contrast, earlier studies have questioned the validity of linear models, but they typically used simplistic models of buildings and/or extremely intense GMs.

A sequential object-oriented framework is extended for parallel processing using an Actor programming model. The paper presents results showing the performance improvements that can be obtained on a network of workstations.

Recently, two members of a new family of Ca2+channel α1 subunits, α1G (or CavT.1) and α1H (or CavT.2), have been cloned and expressed. These α1 subunits generate Ba2+currents similar to the T-type Ca2+currents present in sensory neurons. Here, we use three methods to investigate whether the T currents of nodosus ganglion neurons are encoded by members of the CavT family. PCR detected the presence of mRNA encoding both α1G and α1H, as well as a third highly related sequence, α1I.In situhybridizations performed on nodosus ganglia demonstrate a high expression of α1H subunit RNAs. Transfection of nodosus ganglion neurons with a generic antisense oligonucleotide against this new α1 subunit family selectively suppresses the low-voltage-activated Ca2+current. The antisense oligonucleotide effect increased with time after transfection and reached a maximum 3 d after treatment, indicating a 2–3 d turnover for the α1 proteins. Taken together, these results suggest that the T-type current present in the sensory neurons is mainly attributable to α1H channels. In addition, taking advantage of the high specificity of the antisense ON to the cloned channels, we showed that T-type currents greatly slowed the repolarization occurring during an action potential and were responsible for up to 51% of the Ca2+entry during spikes. Therefore, the antisense strategy clearly demonstrates the role of low-voltage-activated Ca2+current in affecting the afterpotential properties and influencing the cell excitability. Such tools should be beneficial to further studies investigating physiological roles of T-type Ca2+currents.

DA - 20020515IS - 1462-0324 (Print)LA - engPT - Case ReportsPT - LetterRN - 0 (Antibodies, Antineutrophil Cytoplasmic)SB - AIMSB - IM