Complexity and Inapproximability Results for Parallel Task Scheduling and Strip Packing

We study the Parallel Task Scheduling problem $Pm|size_j|C_{\max}$ with a constant number of machines. This problem is known to be strongly NP-complete for each $m \geq 5$, while it is solvable in pseudo-polynomial time for each $m \leq 3$. We give a positive answer to the long-standing open question whether this problem is strongly $NP$-complete for $m=4$. As a second result, we improve the lower bound of $\frac{12}{11}$ for approximating pseudo-polynomial Strip Packing to $\frac{5}{4}$. Since the best known approximation algorithm for this problem has a ratio of $\frac{4}{3} + \varepsilon$, this result narrows the gap between approximation ratio and inapproximability result by a significant step. Both results are proven by a reduction from the strongly $NP$-complete problem 3-Partition

Approximation Algorithms for Scheduling Parallel Jobs: Breaking the Approximation Ratio of 2

In this paper we study variants of the non-preemptive parallel job scheduling problem in which the number of machines is polynomially bounded in the number of jobs. For this problem we show that a schedule with length at most (1 + ε)OPT can be calculated in polynomial time. Unless P = NP, this is the best possible result (in the sense of approximation ratio), since the problem is strongly NP-hard. For the case, where all jobs must be allotted to a subset of consecutive machines, a schedule with length at most (1.5 + ε)OPT can be calculated in polynomial time. The previously best known results are algorithms with absolute approximation ratio 2. Furthermore, we extend both algorithms to the case of malleable jobs with the same approximation ratios

SAT0166 BIOMARKERS OF B-CELL DEPLETION AND RESPONSE IN A RANDOMIZED, CONTROLLED TRIAL OF OBINUTUZUMAB FOR PROLIFERATIVE LUPUS NEPHRITIS

Background:Incomplete B-cell and plasmablast depletion, as measured using highly sensitive flow cytometry (HSFC), is associated with lower response rates following rituximab in SLE [1]. Enhanced B-cell depletion with the type II anti-CD20 mAb obinutuzumab resulted in increased renal responses in proliferative lupus nephritis (LN) in the NOBILITY trial (NCT02550652) and will be further evaluated in the Phase 3 REGENCY trial (NCT04221477).Objectives:To measure peripheral B-cells, B-cell subsets (naïve, memory and plasmablast) and B-cell activating factor (BAFF) levels and to assess associations between B-cell depletion and renal response in LN patients in a clinical trial of obinutuzumab.Methods:126 patients with active Class III/IV LN were randomized to obinutuzumab or placebo infusions in combination with mycophenolate and glucocorticoids. Peripheral B-cells were measured using a HSFC method with a lower limit of quantitation of 0.441 cells/μL. Serum levels of BAFF were evaluated using ELISA. Sustained depletion was defined by total B-cells below the limit of detection at both weeks 24 and 52. Renal response definitions from Phase 2 NOBILITY and Phase 3 REGENCY trials were used.Results:Obinutuzumab resulted in rapid and complete depletion of total B-cells, memory and naïve B-cells, and plasmablasts from peripheral blood, with 88% of obinutuzumab patients depleted to 15% from baseline SCr, and 15% from baseline and urinary RBCs not increased > 50% from baseline66%***45%*29%REGENCY complete responseUPCR 25% from baseline SCr69%**45%31%REGENCY overall responseCRR or ≥ 50% reduction in UPCRb with SCr not increased > 25% from baseline84%***55%50%* P < 0.2 vs. placebo group.** P < 0.05 vs. placebo group.*** P < 0.001 vs. placebo group.aEleven patients in the obinutuzumab group with insufficient data to determine depletion status were excluded.b≥ 50% reduction in UPCR to a value < 1 (< 3 if the baseline UPCR was ≥ 3).Acknowledgments :This study was funded by F. Hoffmann-La Roche.Disclosure of Interests: :Edward Vital Grant/research support from: AstraZeneca, Roche/Genentech, and Sandoz, Consultant of: AstraZeneca, GSK, Roche/Genentech, and Sandoz, Speakers bureau: Becton Dickinson and GSK, Philippe Rémy: None declared, Luis Fernando Quintana Porras: None declared, Laurent Chiche: None declared, Dominique Chauveau: None declared, Richard Furie Grant/research support from: AstraZeneca, Biogen, Consultant of: AstraZeneca, Biogen, Thomas Schindler Employee of: F. Hoffmann-La Roche, Jay Garg Employee of: Genentech, Matthew D. Cascino Employee of: Genentech, Zahir Amoura Grant/research support from: GSK, Roche, Consultant of: GSK, Astra Zeneca, Amgen, Andrea Doria Consultant of: GSK, Pfizer, Abbvie, Novartis, Ely Lilly, Speakers bureau: UCB pharma, GSK, Pfizer, Janssen, Abbvie, Novartis, Ely Lilly, BMS, Cary Michael Donna Looney Employee of: Genentech, Dario Roccatello: None declare

IgG4-related diseases: state of the art on clinical practice guidelines

Immunoglobulin G4-related diseases (IgG4-RD) are a group of chronic relapsing-remitting inflammatory conditions, characterised by tissue infiltration with lymphocytes and IgG4-secreting plasma cells, fibrosis and a usually favourable response to steroids. In this narrative review, we summarise the results of a systematic literature research, which was performed as part of the European Reference Network ReCONNET, aimed at evaluating existing clinical practice guidelines (CPGs) and recommendations in IgG4-RD. From 167 publications initially obtained from a systematic literature search, only one was identified as a systematic multispecialist, evidence-based, consensus guidance statement on diagnosis and treatment of IgG4-RD, which may be recommended for use as CPG in IgG4-RD. With the recognition of a limited evidence based in this increasingly recognised disease, the group discussion has identified the following unmet needs: lack of shared classification criteria, absence of formal guidelines on diagnosis, no evidence-based therapeutic recommendations and lack of activity and damage indices. Areas of unmet needs include the difficulties in diagnosis, management and monitoring and the scarcity of expert centre

Euclid preparation. III. Galaxy cluster detection in the wide photometric survey, performance and algorithm selection

Galaxy cluster counts in bins of mass and redshift have been shown to be a competitive probe to test cosmological models. This method requires an efficient blind detection of clusters from surveys with a well-known selection function and robust mass estimates, which is particularly challenging at high redshift. The Euclid wide survey will cover 15 000 deg2 of the sky, avoiding contamination by light from our Galaxy and our solar system in the optical and near-infrared bands, down to magnitude 24 in the H-band. The resulting data will make it possible to detect a large number of galaxy clusters spanning a wide-range of masses up to redshift ∼2 and possibly higher. This paper presents the final results of the Euclid Cluster Finder Challenge (CFC), fourth in a series of similar challenges. The objective of these challenges was to select the cluster detection algorithms that best meet the requirements of the Euclid mission. The final CFC included six independent detection algorithms, based on different techniques, such as photometric redshift tomography, optimal filtering, hierarchical approach, wavelet and friend-of-friends algorithms. These algorithms were blindly applied to a mock galaxy catalog with representative Euclid-like properties. The relative performance of the algorithms was assessed by matching the resulting detections to known clusters in the simulations down to masses of M₂₀₀ ∼ 10^(13.25) M⊙. Several matching procedures were tested, thus making it possible to estimate the associated systematic effects on completeness to 80% completeness for a mean purity of 80% down to masses of 10¹⁴ M⊙ and up to redshift z = 2. Based on these results, two algorithms were selected to be implemented in the Euclid pipeline, the Adaptive Matched Identifier of Clustered Objects (AMICO) code, based on matched filtering, and the PZWav code, based on an adaptive wavelet approach

In Antisynthetase Syndrome, ACPA Are Associated With Severe and Erosive Arthritis: An Overlapping Rheumatoid Arthritis and Antisynthetase Syndrome

International audienceAbstract: Anticitrullinated peptide/protein antibodies (ACPA), which are highly specific for rheumatoid arthritis (RA), may be found in some patients with other systemic autoimmune diseases. The clinical significance of ACPA in patients with antisynthetase syndrome (ASS), a systemic disease characterized by the association of myositis, interstitial lung disease, polyarthralgia, and/or polyarthritis, has not yet been evaluated with regard to phenotype, prognosis, and response to treatment. ACPA-positive ASS patients were first identified among a French multicenter registry of patients with ASS. Additionally, all French rheumatology and internal medicine practitioners registered on the Club Rhumatismes et Inflammation web site were asked to report their observations of ASS patients with ACPA. The 17 collected patients were retrospectively studied using a standardized questionnaire and compared with 34 unselected ACPA-negative ASS patients in a case–control study. All ACPA-positive ASS patients suffered from arthritis versus 41% in the control group (P 7-year mean follow-up, extra-articular outcomes and survival were not different. ACPA-positive ASS patients showed an overlapping RA–ASS syndrome, were at high risk of refractory erosive arthritis, and might experience ASS flare when treated with antitumor necrosis factor drugs. In contrast, other biologics such as anti-CD20 mAb were effective in this context, without worsening systemic involvements

Exhausted Cytotoxic Control of Epstein-Barr Virus in Human Lupus

Systemic Lupus Erythematosus (SLE) pathology has long been associated with an increased Epstein-Barr Virus (EBV) seropositivity, viremia and cross-reactive serum antibodies specific for both virus and self. It has therefore been postulated that EBV triggers SLE immunopathology, although the mechanism remains elusive. Here, we investigate whether frequent peaks of EBV viral load in SLE patients are a consequence of dysfunctional anti-EBV CD8+ T cell responses. Both inactive and active SLE patients (n = 76 and 42, respectively), have significantly elevated EBV viral loads (P = 0.003 and 0.002, respectively) compared to age- and sex-matched healthy controls (n = 29). Interestingly, less EBV-specific CD8+ T cells are able to secrete multiple cytokines (IFN-γ, TNF-α, IL-2 and MIP-1β) in inactive and active SLE patients compared to controls (P = 0.0003 and 0.0084, respectively). Moreover, EBV-specific CD8+ T cells are also less cytotoxic in SLE patients than in controls (CD107a expression: P = 0.0009, Granzyme B release: P = 0.0001). Importantly, cytomegalovirus (CMV)-specific responses were not found significantly altered in SLE patients. Furthermore, we demonstrate that EBV-specific CD8+ T cell impairment is a consequence of their Programmed Death 1 (PD-1) receptor up-regulation, as blocking this pathway reverses the dysfunctional phenotype. Finally, prospective monitoring of lupus patients revealed that disease flares precede EBV reactivation. In conclusion, EBV-specific CD8+ T cell responses in SLE patients are functionally impaired, but EBV reactivation appears to be an aggravating consequence rather than a cause of SLE immunopathology. We therefore propose that autoimmune B cell activation during flares drives frequent EBV reactivation, which contributes in a vicious circle to the perpetuation of immune activation in SLE patients

A 1-Year Prospective French Nationwide Study of Emergency Hospital Admissions in Children and Adults with Primary Immunodeficiency.

PURPOSE: Patients with primary immunodeficiency (PID) are at risk of serious complications. However, data on the incidence and causes of emergency hospital admissions are scarce. The primary objective of the present study was to describe emergency hospital admissions among patients with PID, with a view to identifying "at-risk" patient profiles. METHODS: We performed a prospective observational 12-month multicenter study in France via the CEREDIH network of regional PID reference centers from November 2010 to October 2011. All patients with PIDs requiring emergency hospital admission were included. RESULTS: A total of 200 admissions concerned 137 patients (73 adults and 64 children, 53% of whom had antibody deficiencies). Thirty admissions were reported for 16 hematopoietic stem cell transplantation recipients. When considering the 170 admissions of non-transplant patients, 149 (85%) were related to acute infections (respiratory tract infections and gastrointestinal tract infections in 72 (36%) and 34 (17%) of cases, respectively). Seventy-seven percent of the admissions occurred during winter or spring (December to May). The in-hospital mortality rate was 8.8% (12 patients); death was related to a severe infection in 11 cases (8%) and Epstein-Barr virus-induced lymphoma in 1 case. Patients with a central venous catheter (n = 19, 13.9%) were significantly more hospitalized for an infection (94.7%) than for a non-infectious reason (5.3%) (p = 0.04). CONCLUSION: Our data showed that the annual incidence of emergency hospital admission among patients with PID is 3.4%. The leading cause of emergency hospital admission was an acute infection, and having a central venous catheter was associated with a significantly greater risk of admission for an infectious episode