Nb3_3Sn conductor development and characterization for NED

The main purpose of Next European Dipole (NED) project is to design and to build an Nb$_{3}$Sn ~ 15 T dipole magnet. Due to budget constraints, NED is mainly focused on superconducting cable development and production. In this work, an update is given on the NED conductor development by Alstom-MSA and SMI, which uses, respectively, Internal-Tin-Diffusion and Powder-In-Tube methods, with the aim of reaching a non-copper critical current density of ~ 3000 A/mm2 at 12 T and 4.2 K. Characterization results, including critical current and magnetization data, are presented and discussed, as well, for conductors already developed by both companies for this project. SMI succeeded to produce a strand with 50 µm diameter filaments and with a critical current of ~ 1400 A at 4.2 K and 12 T, corresponding to a non-copper critical current density of ~ 2500 A/mm2. Cabling trials with this strand were successfully carried out at LBNL

Status of the LHC Superconducting Cable Mass Production

Six contracts have been placed with industrial companies for the production of 1200 tons of the superconducting (SC) cables needed for the main dipoles and quadrupoles of the Large Hadron Collider (LHC). In addition, two contracts have been placed for the supply of 470 tons of NbTi and 26 tons of Nb sheets. The main characteristic of the specification is that it is functional. This means that the physical, mechanical and electrical properties of strands and cables are specified without defining the manufacturing processes. Facilities for the high precision measurements of the wire and cable properties have been implemented at CERN, such as strand and cable critical current, copper to superconductor ratio, interstrand resistance, magnetisation, RRR at 4.2 K and 1.9 K. The production has started showing that the highly demanding specifications can be fulfilled. This paper reviews the organisation of the contracts, the test facilities installed at CERN, the various types of measurements and the results of the main physical properties obtained on the first batches. The status of the deliveries is presented

Summary of the Test Results of ITER Conductors in SULTAN

Abstract. After completing the qualification tests of the ITER cable-in-conduit conductors (CICC), the tests of samples from the series manufacture are running in the SULTAN test facility in Villigen, Switzerland. The key test for the conductor samples is the current sharing temperature, Tcs, at the nominal operating field and current, i.e. the maximum temperature at which the conductors operate before developing an electric field of 10 μV/m. All the TF samples fulfilled the ITER requirement of Tcs ≥ 5.8 K after 1000 load cycles. The Tcs results have a broad scattering among the suppliers, from 5.8 K up to 6.6 K. The assembly of the Nb3Sn based CICC samples (for TF and CS coils) is carried out at CRPP. The NbTi CICC samples (for PF, CC and bus bars) are assembled at the suppliers, with a U-bend replacing the bottom joint. The poor performance of some Main Busbar (MB) conductor samples, caused by poor sample assembly, triggered the effort to assemble a MB sample at CRPP with solder filled terminations and a bottom joint. The superior test results of the MB-CRPP sample, closely matching the performance assessment carried out using 3-D field distribution and n-index behavior was a successful achievement of the last year of operation. According to the Procurement Arrangement for the ITER coils, the winding companies must qualify the joint and termination manufacture by SULTAN samples. The first joint sample tested in SULTAN was a TF joint from EU, followed by a Correction Coil (CC) joint sample from China. Other joint samples are being assembled in USA (Central Solenoid), in Russia (PF1), in EU (PF2 - PF5) and in China (PF6). All the ITER coils use the “twin box” design for joints, except the Central Solenoid. At the first test in SULTAN of a twin-box TF joint sample in 2013, an unexpected resistance increase was observed after an accidental dump of the SULTAN field, causing a large field transient parallel to the joint contact surface, with large eddy currents and electromagnetic loads at the pressure-contact between strand bundle and copper plate of the twin box. The resistance requirement for the TF joint was still fulfilled after the dump. The initial performance of the joint sample for Correction Coil conductor was not satisfactory and a second qualification sample is being prepared

Clinical and immunologic phenotype associated with activated phosphoinositide 3-kinase δ syndrome 2: A cohort study

Background Activated phosphoinositide 3-kinase δ syndrome (APDS) 2 (p110δ-activating mutations causing senescent T cells, lymphadenopathy, and immunodeficiency [PASLI]–R1), a recently described primary immunodeficiency, results from autosomal dominant mutations in PIK3R1, the gene encoding the regulatory subunit (p85α, p55α, and p50α) of class IA phosphoinositide 3-kinases. Objectives We sought to review the clinical, immunologic, and histopathologic phenotypes of APDS2 in a genetically defined international patient cohort. Methods The medical and biological records of 36 patients with genetically diagnosed APDS2 were collected and reviewed. Results Mutations within splice acceptor and donor sites of exon 11 of the PIK3R1 gene lead to APDS2. Recurrent upper respiratory tract infections (100%), pneumonitis (71%), and chronic lymphoproliferation (89%, including adenopathy [75%], splenomegaly [43%], and upper respiratory tract lymphoid hyperplasia [48%]) were the most common features. Growth retardation was frequently noticed (45%). Other complications were mild neurodevelopmental delay (31%); malignant diseases (28%), most of them being B-cell lymphomas; autoimmunity (17%); bronchiectasis (18%); and chronic diarrhea (24%). Decreased serum IgA and IgG levels (87%), increased IgM levels (58%), B-cell lymphopenia (88%) associated with an increased frequency of transitional B cells (93%), and decreased numbers of naive CD4 and naive CD8 cells but increased numbers of CD8 effector/memory T cells were predominant immunologic features. The majority of patients (89%) received immunoglobulin replacement; 3 patients were treated with rituximab, and 6 were treated with rapamycin initiated after diagnosis of APDS2. Five patients died from APDS2-related complications. Conclusion APDS2 is a combined immunodeficiency with a variable clinical phenotype. Complications are frequent, such as severe bacterial and viral infections, lymphoproliferation, and lymphoma similar to APDS1/PASLI-CD. Immunoglobulin replacement therapy, rapamycin, and, likely in the near future, selective phosphoinositide 3-kinase δ inhibitors are possible treatment options

Campylobacter infection in adult patients with primary antibody deficiency

International audiencePrimary antibody deficiency (PAD) is characterized by a defective immunoglobulin production and recurrent infections, mostly involving respiratory and gastrointestinal tracts. Chronic or recurrent diarrhea is reported in up to 23%. Campylobacter infection is a common cause of infectious diarrhea, reported in 1.2% to 7.5% of patients with common variable immunodefi-ciency (CVID), the most frequent PAD. The aim of this study was to describe Campylobacter infection in patients with PAD included in a large nationwide study and analyze factors associ-ated with susceptibility to this pathogen. The DEFI (DEFicit Immunitaire) study is an ongoing large cross-sectional French multicentric study of adults with PAD, with retrospective collection of clinical data. All patients with a history of bacteriologically documented Campylobacter infection were identified, and clinical data were collected for each episode. Factors associated with recurrent infection were assessed as oddsratio (OR) and 95% confidence interval (CI), calculated by means of simple regression analysis. In patients with available material, strains of each episode were characterized using molecular analysis and compared (Table E1, available in this article’s Online Repository at www.jaci-inpractice.org). A com-parison of immunodeficiency-related characteristics of patients with and without Campylobacter infection was performed in the homogeneous group of patients with CVID. The control group included patients with CVID from DEFI centers who confirmed that patients did not develop Campylobacter infection after enrollment (Figure E1, available in this article’s Online Repository at www.jaci-inpractice.org). After correction for multiple comparisons, P<.016 was considered significant. Since 2004, 790 patients with PAD were included in the DEFI study, and 51 presented with Campylobacter infection (6.5%). Medical chart was available for review in 45 patients. Characteristics of these patients at the time of enrollment in the DEFI study are detailed in Table E2 (available in this article’s Online Repository at www.jaci-inpractice.org). A total of 97 episodes were recorded (Table I). The overall distribution of Campylobacter species was unremarkable. Antimicrobial susceptibility testing revealed a higher resistance rate than in the general population for each antibiotic tested (see Figure E2, available in this article’s Online Repository at www.jaci-inpractice.org). A comorbidity was present in 55% of Campylobacter episodes, and a coinfection by other enteropathogens in 10%. Most patients were receiving concomitant therapy at the time of episode. One patient with end-stage cirrhosis died with Campylobacter bacteremia. Overall, bacteremia was observed in 24 episodes (13 patients) and was associated with extraintestinal complication in 10 episodes. Nineteen patients (42%) presented with recurrent (2-11) episodes. Factors associated with recurrent episodes were the presence of comorbidity (OR, 3.7 [95% CI, 1.1-13.1]) and undetectable serum IgA (OR, 8.6 [95% CI, 1.1-21.2]). None of these factors remain significant in multivariate analysis. A mo- lecular study of a subset of 18 strains from 5 patients with recurrent infections demonstrated that all strains were different, even when the antimicrobial susceptibility testing was similar and when the episodes occurred closely over time (Figure E3, available in this article’s Online Repository at www.jaci-inpractice.org). Compared with 288 patients with CVID without Campylobacter infection, patients with CVID with Campylo-bacter infection presented a higher prevalence of consanguinity and a more severe CVID phenotype, with more frequent disease- related complications, lower serum immunoglobulin levels, lower B and natural killer (NK) cells, and a trend for lower naive CD4þT cell at the time of enrollment in the DEFI study (Table II). This study is the first description of a large series of patients with PAD and Campylobacter infection. The 6.5% prevalence was probably underestimated because of the retrospective nature of the clinical data collection. In this population, symptoms were mostly restricted to an isolated, frequently severe, chronic watery diarrhea, with associated malnutrition, leading to repeated hospitalizations and impaired quality of life. Other digestive symptoms and fever were less frequent than those observed in the general population. In contrast, bacteremia and extra- digestive localizations were more frequent (25% vs 0.15% to 2%, and 22% vs 7%, respectively). Despite frequent hospitalizations, the overall prognosis was good. Recurrence rate was high (42%) compared with 1.2% in the general population, and was associated with extraintestinal comorbidity and unde- tectable IgA level in univariate analysis. Although limited by the number of available strains, molecular profiles of strains from patients with recurrent infections were all different. Thus, we could hypothesize that reinfection is more likely than persistent colonization, although colonization with multiple strains cannot be excluded. Conditions associated with the occurrence of Campylobacter infection were described in an analysis restricted to a large ho- mogeneous group of 325 patients with CVID. The present data suggest that hypochlorhydria, either proton pump inhibitor (PPI)-induced or associated with autoimmune gastritis, might play an important role in the pathogenesis of this infection. Almost all CVID-associated complications, particularly liver and gastrointestinal disease, were more frequent in patients with Campylobacter infection. A more severe immune deficiency at CVID diagnosis, with a lower serum immunoglobulin level, was also observed. Even in patients with immunoglobulin replacement therapy, IgM and IgA levels remain very low. IgA and IgM, almost absent in immunoglobulin batches, are more important than IgG in Campylobacter immunity. B-cell and specifically switch memory B-cell deficiency was also more severe in patients with CVID with Campylobacter infection than in patients without Campylobacter infection. This is in line with the high prevalence of Campylobacter infection observed in Good syndrome and X-linked agammaglobulinemia, 2 conditions associated with no circulating B cells (Figure E1, available in this article’s Online Repository at www.jaci-inpractice.org). B cells are also known to be important for the dialogue between the immune system and gut microbiota, whose composition is important for Campylobacter immunity. T cells may also play an important role, with a trend for decreased naive T cells. Indeed, 15 patients (40%) presented with a severe associated T-cell defect and could be considered as late-onset combined im-munodeficiency (data not shown). In patients with PAD, Campylobacter infection is quite frequent and seems to be related to various factors adding up together: severity of the immune deficiency, PAD complication, and associated antibiotics, immunosuppressive therapies, and PPI. It is characterized by a high frequency of recurrence and bacteremia. Recurrence is associated with the presence of comorbidity and IgA defect, and turned out to be due to rein- fection more than to persistent colonization, suggesting a specific susceptibility despite immunoglobulin substitution

Genetic analysis of patients with Fuchs endothelial corneal dystrophy in India

<p>Abstract</p> <p>Background</p> <p>Mutations in <it>COL8A2 </it>gene which encodes the collagen alpha-2 (VIII) chain have been identified in both familial and sporadic cases of Fuchs endothelial corneal dystrophy (FECD). Heterozygous mutations in the <it>SLC4A11 </it>gene are also known to cause late-onset FECD. Therefore we screened for <it>COL8A2</it>, <it>SLC4A11 </it>gene variants in Indian FECD patients.</p> <p>Methods</p> <p>Eighty patients with clinically diagnosed FECD and 100 age matched normal individuals were recruited. Genomic DNA was isolated from peripheral blood leukocytes. Mutations in <it>COL8A2</it>, <it>SLC4A11 </it>coding regions were screened using bi-directional sequencing. Fischer's exact test or Pearson's chi squared test were used to predict the statistical association of genotypes with the phenotype.</p> <p>Results</p> <p>Screening of <it>COL8A2 </it>gene revealed 2 novel c.1610G>A, c.1643A>G and 3 reported variations c.112G>A, c.464G>A and c.1485G>A. In <it>SLC4A11 </it>gene, novel c.1659C>T, c.1974C>T and reported c.405G>A, c.481A>C and c.639G>A variants were identified. However all the variations in both the genes were also present in unaffected controls.</p> <p>Conclusions</p> <p>This is the first study analysing <it>COL8A2 </it>gene in Indian patients with FECD. No pathogenic mutations were identified in <it>COL8A2</it>. Merely silent changes, which showed statistically insignificant association with FECD, were identified in the screening of <it>SLC4A11 </it>gene. These results suggest that <it>COL8A2</it>, <it>SLC4A11 </it>genes may not be responsible for FECD in patients examined in this study.</p