The ATLAS Muon Drift Tube (MDT) ReadOut Drivers (MROD) have been in operation for more than 15 years and are expected to remain in operation until about 2026. In the event of extensive failures the number of spare modules may be insufficient. This project therefore proposes using the Front-End LInk eXchange (FELIX) system, a new component of the ATLAS data acquisition (DAQ) infrastructure, to overcome a potential MROD failure. The presentation will describe the FELIX-MROD’s design as well as tests of its functionality. The latest results of testing its integration into the ATLAS DAQ will be reported.

Aim: Patients with secondary immunodeficiency (SID) are at increased risk of infections and may be treated with immunoglobulin replacement therapy (IgRT). Despite growing efficacy evidence for IgRT in infection prevention in SID, treatment guidelines are not aligned. Materials & methods: A retrospective database analysis was conducted to assess treatment patterns and infection rates in patients at risk of SID-related infections, with or without IgRT (IgPro10) exposure, to evaluate real-world effectiveness of IgRT in infection prevention. Results: Of 11,448 patients included, 222 received IgPro10. B-cell malignancies and solid organ transplants were the predominant underlying conditions. Despite being sicker at baseline, the IgPro10 cohort demonstrated fewer infections post-index than the non-IgRT cohort. Conclusion: IgPro10 may be an effective option for infection prevention in SID.

ObjectiveThis open‐label 12‐week study was conducted to evaluate the efficacy and safety of tofacitinib, a JAK inhibitor, in treatment‐refractory active dermatomyositis (DM).MethodsTofacitinib in extended‐release doses of 11 mg was administered daily to 10 subjects with DM. Prior to treatment, a complete washout of all steroid‐sparing agents was performed. The primary outcome measure was assessment of disease activity improvement based on the International Myositis Assessment and Clinical Studies group definition of improvement. Response rate was measured as the total improvement score according to the 2016 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) myositis response criteria. Secondary outcome measures included Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) scores, chemokine levels, immunohistochemical analysis of STAT1 expression in the skin, RNA sequencing analysis, and safety.ResultsAt 12 weeks, the primary outcome was met in all 10 subjects. Five (50%) of 10 subjects experienced moderate improvement in disease activity, and the other 50% experienced minimal improvement according to the 2016 ACR/EULAR myositis response criteria. The secondary outcome of the mean change in the CDASI activity score over 12 weeks was statistically significant (mean ± SD 28 ± 15.4 at baseline versus 9.5 ± 8.5 at 12 weeks) (P = 0.0005). Serum chemokine levels of CXCL9/CXCL10 showed a statistically significant change from baseline. A marked decrease in STAT1 signaling in association with suppression of interferon target gene expression was demonstrated in 3 of 9 skin biopsy samples from subjects with dermatomyositis. The mean ± SD level of creatine kinase in the 10 subjects at baseline was 82 ± 34.8 IU/liter, highlighting that disease activity was predominantly located in the skin.ConclusionThis is the first prospective, open‐label clinical trial of tofacitinib in DM that demonstrates strong clinical efficacy of a pan‐JAK inhibitor, as measured by validated myositis response criteria. Future randomized controlled trials using JAK inhibitors should be considered for treating DM.

We previously demonstrated that tofacitinib was effective in treating skin-predominant refractory dermatomyositis (DM) at 12 weeks in a prospective open label clinical trial, Study of Tofacitinib In Refractory dermatomyositis (STIR) (1). Here, we report the long-term extension results of up to 96 weeks to investigate the treatment durability of tofacitinib in refractory DM. Inclusion criteria and outcome measures were the same as the parent study (1). Assessments were conducted at weeks 20, 72, and 96. The baseline demographic features of all 10 trial patients were reported previously (1).

Abstract Secondary immunodeficiency (SID) is an acquired condition caused by several factors including, but not limited to, B-cell malignancies, and may result in frequent, burdensome, and possibly life-threatening infections. Treatment guidelines recommend immunoglobulin replacement therapy (IgRT) in certain settings to prevent recurrent, persistent, or major (severe) infections. This retrospective analysis of a US healthcare database characterized patients (pts) with suspected SID, who experienced infections, and were or were not treated with IgRT (IgPro10 [Privigen ®]). Data were collected from 26 US healthcare organizations from TriNetX DataWorks™ Network between 1/1/09 - 1/31/20. Pts were required to have the following: suspected SID (defined as ≥1 underlying conditions related to SID such as: solid organ transplant [SOT], non-Hodgkin lymphoma [NHL], multiple myeloma [MM], and chronic lymphocytic leukemia [CLL]), ≥1 severe infection (defined as requiring hospitalization and/or treatment with intravenous antibiotics or anti-viral medication) or ≥2 non-severe infections between underlying condition diagnosis date and the index date, the absence of diagnosed primary immunodeficiency, and an available medical history of ≥12 months pre-index and ≥3 months post-index. The index date refers to first IgPro10 use or the corresponding date for pts not receiving IgPro10 (unexposed cohort). In the IgPro10 cohort, pts were required to have had ≥2 consecutive IgPro10 administrations within 90 days. Between the pre- and post-index periods, the following variables were compared for both cohorts: pts' treatment, underlying conditions, baseline characteristics, and change in annualized infection rate (for infections of any severity and severe infections). Pre-index immunoglobulin G (IgG) (or calculated globulin [CG]) levels were recorded as: hypogammaglobulinemia (HGG) (IgG <6 g/L or CG <18 g/L), normal (IgG ≥6 g/L or CG ≥18 g/L), or missing. A generalized estimation equation (GEE) model with logit link was used to compare the change in the proportion of pts with an annualized infection rate of zero from the pre- to the post-index period across both cohorts. The final sample comprised 222 IgPro10 pts and 11,226 unexposed pts. In the IgPro10 cohort, 143 pts were on IgPro10 for <6 months, 41 pts for 6-12 months, and 38 pts for >12 months. In both the IgPro10 and the unexposed cohorts, SOT was the most frequent underlying condition (45.5% and 44.6%, respectively), followed by NHL (21.6% and 28.2%, respectively), MM (14.4% and 10.1%, respectively), and CLL (11.3% and 7.6%, respectively). Age (mean [SD], 57.2 [13.9] vs 57.9 [17.0] years old, respectively) and sex distribution (male:female, 56.3%:43.7% vs 51%:48.8%, respectively) were similar in the IgPro10 and unexposed cohort. During the pre-index period, the IgPro10 cohort, compared with the unexposed cohort, received a greater number of antibiotic courses (median [interquartile range], 7 [20] vs 1 [5], respectively), had a substantially higher proportion of pts with HGG (HGG: 34.7% vs 3.0%; normal IgG: 43.7% vs 57.8%; missing: 21.6% vs 39.2%, respectively), and a lower proportion of pts with an annualized infection rate of zero (for infections of any severity and severe infections) (Figure 1). There was an approximate four-fold increase in the proportion of pts with no infections of any severity following IgPro10 administration; this increase was significantly larger than in the unexposed cohort (p<0.0001) (Figure 1). Additionally, there was an increase in the proportion of pts with no severe infections following IgPro10 administration. Again, this increase was significantly larger than in the unexposed cohort (p<0.0001) (Figure 1). This real-world study found that compared with pts not receiving IgRT, pts who subsequently went on to receive IgPro10 experienced more infections pre-treatment. Following IgPro10 administration, more pts had an annualized infection rate of zero (for infections of any severity or severe infections) compared with the pre-index period. Moreover, the increase in the proportion of pts with no infections was greater in the IgPro10 cohort than in the unexposed cohort, for both infections of any severity and severe infections. Taken together, these findings suggest effectiveness of IgPro10 in pts with SID, but further study, such as a prospective randomized controlled trial, is needed to confirm these initial findings. Figure 1 Figure 1. Disclosures Lahue: CSL Behring: Consultancy; Alkemi Health: Current Employment, Current holder of stock options in a privately-held company. Mallick: CSL Behring: Current Employment, Current holder of individual stocks in a privately-held company. Zhang: CSL Behring: Current Employment, Current holder of individual stocks in a privately-held company. Koenig: CSL Behring: Current Employment, Current holder of individual stocks in a privately-held company. Espinoza: CSL Behring: Current Employment, Current holder of individual stocks in a privately-held company. OffLabel Disclosure: IgPro10 (Privigen®, CSL Behring, King of Prussia, PA, U.S.), a type of immunoglobulin replacement therapy, is currently approved in the U.S. to treat patients with primary immunodeficiency (PI), chronic inflammatory demyelinating polyneuropathy (CIDP), and chronic immune thrombocytopenic purpura (ITP).

Abstract Background The relevance of an angiosome model for infrapopliteal endovascular interventions (EVT) in diabetic patients is still in debate because the lesions are more likely to be diffuse with a different pattern of collateral arteries ranging from reduced to normal caliber. The aim of this study was to analyse the outcome of two different endovascular infrapopliteal interventional strategies (Group I: angiosome-based direct revascularization -DR- vs. Group II: complete (direct + indirect) revascularization strategy -CR-) in diabetic patients with critical limb ischemia. Furthermore we analyzed the outcome if DR or CR failed and only indirect revascularization (IR) or no revascularization was possible. Both groups were differentiated in patients with collaterals, defined as an intact pedal arch (immediate or after pedal PTA). Patients and methods We performed a prospective cohort study in routine angiologic patients. The database includes 91 consecutive EVT with two intrapopliteal interventional strategies performed in 68 diabetic patients (pts.; 24 female, 44 male, mean age 73±10 years) between 2013–2015 and 2016–2019. The study included only patients with CLI (Rutherford class 4 or greater) with a critical subtotal stenosis or occlusion of at least one artery below the knee. EVT were performed mainly by an antegrade approach and with the use of 5F sheaths. In case of failure to recanalise, a retrograde approach was attempted. Positive clinical outcome was defined as wound healing without amputation or wound healing after minor amputation, combined with a symptom improvement to Rutherford category 0 or 1 after 6 months. The clinical outcome proportions were compared using the Fisher's exact test. Results An angiosome-based direct reperfusion (DR) of the artery supplying the ischemic tissue and a complete (both direct and indirect, CR) revascularization strategy demonstrated a similar positive clinical outcome (92,6% vs. 90,5%; p=0.594). Indirect revascularization showed a significantly lower positive outcome in comparison to a successful DR as well as CR strategy (33,3% vs 92,6%, p=0.0003; 40% vs 90,5%, p=0.001). IR outcome improved by the presence of collaterals (66,7% vs. 30,8%). Conclusions In case of successful intervention, both strategies (DR and CR) yielded a similarly high proportion of positive clinical outcome. The role of collaterals and the pedal arch are important for the clinical outcome in patients in whom only indirect revascularization was possible, because of unsuccessful CR or DR. The time of the procedure/radiation, the risk to reopen more than one vessel, the necessary amount of contrast medium and final the costs of the procedure should also be considered for an individually based decision process to perform an angiosome-based direct or a complete revascularization. Funding Acknowledgement Type of funding source: None

MedAustron is a hadron synchrotron primarily designed and built for tumor treatment. Besides its clinical purpose, it is equipped with a dedicated beam line for non-clinical research. This beam line can be used for beam tests utilizing protons with an energy up to 252.7MeV at the moment, but 800 MeV protons and carbon ions will become available through 2019. We conducted first beam tests at MedAustron in order to understand the usability of this beam line for testing silicon detectors. This includes the design and commissioning of a trigger setup based on scintillators and PMTs, which is meant to stay permanently there. This allowed us to measure energy deposition utilizing silicon strip sensors read out by the ALiBaVa system. Nominal beam energies were varied between 62.4 and 252.7 MeV and verified by determining the specific energy loss of protons in silicon. As these energies are rather low compared to typical HEP beam tests, the proton beam through the setup was simulated to determine the necessary energy correction due to losses through matter and air in front of the Si sensor. These approaches yielded good agreement with reference data from NIST, so MedAustron is considered as a reliable facility for future beam tests.

The production cross-sections for W +/- and Z bosons are measured using ATLAS data corresponding to an integrated luminosity of 4.0 pb-1 collected at a centre-ofmass energy v s = 2.76 TeV. The deca ...

Abstract Background The objective of this study was to evaluate early changes in magnetic resonance imaging (MRI) and clinical disease activity measures as predictors of later structural progression in early rheumatoid arthritis (RA). Methods This was a post hoc analysis of data pooled across treatments from a three-arm (tofacitinib monotherapy, tofacitinib with methotrexate [MTX], or MTX monotherapy) trial of MTX-naïve patients with early, active RA. Synovitis, osteitis and erosions were assessed with the Outcome Measures in Rheumatology (OMERACT) RA MRI scoring system (RAMRIS) and RAMRIQ (automated quantitative RA MRI assessment system; automated RAMRIS) at months 0, 1, 3, 6 and 12. Radiographs were assessed at months 0, 6 and 12, and clinical endpoints were assessed at all timepoints. Univariate and multivariate analyses explored the predictive value of early changes in RAMRIS/RAMRIQ parameters and disease activity measures, with respect to subsequent radiographic progression. Results Data from 109 patients with a mean RA duration of 0.7 years were included. In univariate analyses, changes in RAMRIS erosions at months 1 and 3 significantly predicted radiographic progression at month 12 (both p < 0.01); changes in RAMRIQ synovitis and osteitis at months 1 and 3 were significant predictors of RAMRIS erosions and radiographic progression at month 12 (all p < 0.01). In subsequent multivariate analyses, RAMRIS erosion change at month 1 (p < 0.05) and RAMRIQ osteitis changes at months 1 and 3 (both p < 0.01) were significant independent predictors of radiographic progression at month 12. Univariate analyses demonstrated that changes in Clinical Disease Activity Index (CDAI) and Disease Activity Score in 28 joints, erythrocyte sedimentation rate (DAS28-4[ESR]) at months 1 and 3 were not predictive of month 12 radiographic progression. Conclusions MRI changes seen as early as 1 month after RA treatment initiation have the potential to better predict long-term radiographic progression than changes in disease activity measures. Trial registration ClinicalTrials.gov, NCT01164579.

Objectives: To determine whether C-reactive protein (CRP) level is predictive of response to tumor necrosis factor-alpha blocker treatment in patients with ankylosing spondylitis (AS) and whether there is an optimal CRP range for treatment initiation. Methods: In this post hoc analysis, data on etanercept-treated patients with AS were pooled from four randomized trials. Week 12 responses (ASAS20, ASAS50, ASDAS-CRP < 1.3, and ASDAS-CRP Delta <= 1.1) were evaluated in relationship to baseline CRP levels (normal, defined as < upper limit of normal [<= ULN]; elevated, > ULN; high, > ULN and <= 3xULN; and very high, > 3xULN), baseline levels of patient-reported outcomes (PROs), and CRP levels at weeks 2, 4, and 8, using univariate and stepwise predictor analyses. In addition, relationships between baseline CRP and other baseline predictors were analyzed using stepwise models of response. Results: Among 867 patients, baseline CRP levels were normal in 371 (43%) patients, high in 299 (34%), and very high in 197 (23%). Very high baseline CRP was a significant predictor for all four week-12 outcomes, compared with normal CRP. Conversely, normal CRP at weeks 2, 4, and 8 was a stronger predictor of week 12 response than elevated CRP. PROs were less consistent predictors of response. In addition, there was a significant association between higher baseline CRP and lower age of disease onset (< 40 years) and between normal CRP and lower disease burden. Conclusions: In patients with AS, both baseline and post-baseline CRP levels can be predictive of response to treatment at week 12, more consistently than PROs. (C) 2018 Elsevier Inc. All rights reserved.

A search for resonancelike structures in the Bs0π± invariant mass spectrum is performed using proton-proton collision data collected by the CMS experiment at the LHC at s=8  TeV, corresponding to an integrated luminosity of 19.7  fb-1. The Bs0 mesons are reconstructed in the decay chain Bs0→J/ψϕ, with J/ψ→μ+μ- and ϕ→K+K-. The Bs0π± invariant mass distribution shows no statistically significant peaks for different selection requirements on the reconstructed Bs0 and π± candidates. Upper limits are set on the relative production rates of the X(5568) and Bs0 states times the branching fraction of the decay X(5568)±→Bs0π±. In addition, upper limits are obtained as a function of the mass and the natural width of possible exotic states decaying into Bs0π±.

A new CMS Tracker is under development for operation at the High Luminosity LHC from 2026 onwards. It includes an outer tracker based on dedicated modules that will reconstruct short track segments, called stubs, using spatially coincident clusters in two closely spaced silicon sensor layers. These modules allow the rejection of low transverse momentum track hits and reduce the data volume before transmission to the first level trigger. The inclusion of tracking information in the trigger decision is essential to limit the first level trigger accept rate. A customized front-end readout chip, the CMS Binary Chip (CBC), containing stub finding logic has been designed for this purpose. A prototype module, equipped with the CBC chip, has been constructed and operated for the first time in a 4 GeV/c positron beam at DESY. The behaviour of the stub finding was studied for different angles of beam incidence on a module, which allows an estimate of the sensitivity to transverse momentum within the future CMS detector. A sharp transverse momentum threshold around 2 GeV/c was demonstrated, which meets the requirement to reject a large fraction of low momentum tracks present in the LHC environment on-detector. This is the first realistic demonstration of a silicon tracking module that is able to select data, based on the particle's transverse momentum, for use in a first level trigger at the LHC . The results from this test are described here.

The aim was to analyze characteristics that predict remission induction and subsequent loss of remission in patients with moderately active rheumatoid arthritis (RA) who received full-dose combination etanercept plus methotrexate induction therapy followed by reduced-dose etanercept or etanercept withdrawal.

Article history: Received 28 August 2017 Received in revised form 14 November 2017 Accepted 2 December 2017 Available online 6 December 2017 Editor: M. Doser

Front-side biasing is an alternative method to bias a silicon sensor. Instead of directly applying high voltage to the backside, one can exploit the conductive properties of the edge region to bias a detector exclusively via front-side connections. This option can be beneficial for the detector design and might help to facilitate the assembly process of modules. The effective bias voltage is affected by the resistance of the edge region and the sensor current. The measurements of n-in-p sensors performed to qualify this concept have shown that the voltage drop emerging from this resistance is negligible before irradiation. After irradiation, however, the resistivity of the edge region increases with fluence and saturates in the region of 107 Ω cm at fluences above 6 ⋅ 1014 neqcm−2 and an operation temperature of −20 ̂C. The measurements are complemented by TCAD simulations and interpretations of the observed effects.

Background As psoriatic arthritis (PsA) treatment choices continue to expand, it is important to consider patient preferences for treatment modalities for PsA. Involving patients in treatment decisions can influence adherence to treatment and outcomes of therapy. Objective To determine patient preferences for medication attributes prescribed for patients with PsA. Methods A choice-based conjoint survey was mailed to 2800 randomly selected patients with PsA who were enrolled in Humana Medicare and commercial plans. Patients had been diagnosed with PsA between January 1, 2012, and September 30, 2016. The medication attributes included in the survey were the medication route of administration, frequency of administration, ability to reduce daily joint pain and swelling, likelihood of serious infections, improvement in the patient's ability to perform daily activities, achieving clear or almost clear skin, and cost. Hierarchical Bayesian models were used to score patient preferences after adjusting for demographic and clinical characteristics. The mean attribute importance scores were used to rank patient preferences. Results A total of 468 patients (258 with a Medicare plan and 210 with a commercial plan) completed the survey. The top 3 medication attributes for patients in Medicare plans were route of administration, cost, and improvement in the ability to perform daily activities. For patients in commercial plans, the top 3 medication attributes were cost, route of administration, and frequency of administration. Within the top 2 attributes for patients in both plans, the oral route of administration and lower cost were most preferred. Conclusion Medication route of administration and cost were the 2 most important considerations for patients diagnosed with PsA who were enrolled in Medicare or commercial plans with Humana. As PsA treatment choices continue to expand, considering patient preferences may improve patient adherence and treatment outcomes and should be considered when making treatment decisions for this patient population.

Background Tofacitinib is an oral JAK inhibitor for the treatment of RA. A novel automated quantification method for RA MRI-detected pathology using statistical shape modelling technology (RAMRIQ) provides a tool that may be even more responsive than the sensitive RAMRIS semi-quantitative standard.1 Objectives To determine if early changes in RAMRIQ were predictive of subsequent MRI and radiographic damage progression in a study of tofacitinib for the treatment of early RA in methotrexate-naïve patients with minimal radiographic progression. Methods We used data from an exploratory, Phase 2 randomised controlled trial comparing tofacitinib, methotrexate and the combination (n=109) in methotrexate-naïve patients with early active RA.1 All patients met ACR classification criteria for active RA. MRI was performed at baseline and at 1, 3, 6 and 12 months. A single centralised reader read all MRI data; data for each patient were randomised by time point and read in the same sitting. We examined changes in synovitis, osteitis and erosions for RAMRIQ and RAMRIS at 1 and 3 months and performed univariate analyses on their relationship to RAMRIS, RAMRIQ and radiographic progression (modified Total Sharp Score [mTSS]) at 12 months. Results Reduction in RAMRIQ synovitis and osteitis at 1 and 3 months were significantly associated with reduction in RAMRIS erosion progression at 12 months (Table). Improvement in RAMRIQ synovitis and osteitis at 1 and 3 months were also associated with reduction in radiographic progression at 12 months, while RAMRIQ erosions at 1 and 3 months were not significantly associated with radiographic progression (Table). Early changes in RAMRIS erosion at 1 and 3 months were associated with radiographic progression at 12 months (Table). Treatment with tofacitinib alone or in combination with methotrexate was also associated with reduced progression in RAMRIS erosions (p=0.017 and p=0.007, respectively). Conclusions In this study, sensitive automated detection demonstrated that change in synovitis and osteitis predict subsequent RAMRIS erosion and radiographic progression. Treatment with tofacitinib as monotherapy or in combination with methotrexate was also highly predictive of no progression of erosive damage. Because of its enhanced sensitivity, novel quantitative imaging analysis has the potential to change RA clinical trial design where assessing structural damage is an objective. References Conaghan PG et al. Ann Rheum Dis 2016; 75: 1024–1033. Acknowledgements Previously presented at ACR 2016 and reproduced with permission. This study was sponsored by Pfizer Inc. Editorial support was provided by S Morgan of CMC and was funded by Pfizer Inc. Disclosure of Interest P. G. Conaghan Consultant for: AbbVie, Eli Lilly, Flexion, Novartis, Pfizer Inc, Roche, Speakers bureau: AbbVie, Novartis, Roche, M. A. Bowes Employee of: Imorphics Ltd, M. Østergaard Grant/research support from: AbbVie, Centocor, Merck, Consultant for: AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Centocor, Eli Lilly, GSK; Hospira, Janssen, Merck, Mundipharma, Novartis, Novo, Orion, Pfizer Inc, Regeneron, Roche, Schering-Plough, Takeda, UCB, Wyeth, Speakers bureau: AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Centocor, Eli Lilly, GSK; Hospira, Janssen, Merck, Mundipharma, Novartis, Novo, Orion, Pfizer Inc, Regeneron, Roche, Schering-Plough, Takeda, UCB, Wyeth, G. Guillard Employee of: Stryker Co, D. Chapman Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, A. Stein Employee of: Quintiles, J. Andrews Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Z. Xie Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, A. Koenig Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, K. Soma Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, B. Wilkinson Shareholder of: Pfizer Inc, Employee of: Pfizer Inc

The luminosity of the LHC will be increased by a factor of five to seven after the third long shutdown (LS3) scheduled in the mid of the next decade. The significant increase in luminosity along with the limitations of the current Tracker require a complete renewal of the CMS Outer Tracker, the Tracker Phase-2 Upgrade, during the LS3. New types of modules called PS and 2S modules are foreseen offering enhanced functionality and radiation hardness. Milestones in sensor R&D for the 2S modules as well as first characterization results are presented. AC-coupled silicon strip sensors of two vendors, produced on 6-inch as well as on 8-inch wafers, are considered which both are in n-on-p technology. Global as well as single strip parameters were measured providing insights into the quality of the sensors.