Severe Asthma Standard-of-Care Background Medication Reduction With Benralizumab: ANDHI in Practice Substudy

peer reviewedBackground: The phase IIIb, randomized, parallel-group, placebo-controlled ANDHI double-blind (DB) study extended understanding of the efficacy of benralizumab for patients with severe eosinophilic asthma. Patients from ANDHI DB could join the 56-week ANDHI in Practice (IP) single-arm, open-label extension substudy. Objective: Assess potential for standard-of-care background medication reductions while maintaining asthma control with benralizumab. Methods: Following ANDHI DB completion, eligible adults were enrolled in ANDHI IP. After an 8-week run-in with benralizumab, there were 5 visits to potentially reduce background asthma medications for patients achieving and maintaining protocol-defined asthma control with benralizumab. Main outcome measures for non–oral corticosteroid (OCS)-dependent patients were the proportions with at least 1 background medication reduction (ie, lower inhaled corticosteroid dose, background medication discontinuation) and the number of adapted Global Initiative for Asthma (GINA) step reductions at end of treatment (EOT). Main outcomes for OCS-dependent patients were reductions in daily OCS dosage and proportion achieving OCS dosage of 5 mg or lower at EOT. Results: For non–OCS-dependent patients, 53.3% (n = 208 of 390) achieved at least 1 background medication reduction, increasing to 72.6% (n = 130 of 179) for patients who maintained protocol-defined asthma control at EOT. A total of 41.9% (n = 163 of 389) achieved at least 1 adapted GINA step reduction, increasing to 61.8% (n = 110 of 178) for patients with protocol-defined EOT asthma control. At ANDHI IP baseline, OCS dosages were 5 mg or lower for 40.4% (n = 40 of 99) of OCS-dependent patients. Of OCS-dependent patients, 50.5% (n = 50 of 99) eliminated OCS and 74.7% (n = 74 of 99) achieved dosages of 5 mg or lower at EOT. Conclusions: These findings demonstrate benralizumab's ability to improve asthma control, thereby allowing background medication reduction. © 202

Examination of ITER Central Solenoid prototype joints

The ITER Magnet System will be the largest and most challenging integrated superconducting magnet systemever built. For the Central Solenoid (CS), cable–in–conduit - conductors (CICCs) of nearly one kilometre lengthare produced, but still, it will be necessary to connect several lengths together to wind the gigantic 110 tonnescoils. The creation of these superconducting joints is one of the most delicate parts of the assembly. There arethree types of ITER CS joints: splice joints, coaxial joints and twin–box joints. US ITER, the ITER DomesticAgency of the USA produced a prototype containing all three types of joints. The goal is to test the performanceof the joints in the SULTAN facility of the Swiss Plasma Center (SPC), capable of reproducing close–to–serviceconditions: high magneticfield (up to 11 T backgroundfield), high current (up to 100 kA) and high massflowrate of supercritical helium for cooling. The paper describes the results of a comprehensive examination cam-paign aimed at understanding the relation between fabrication and performance of the CS prototype joints. Thetest campaign combines advanced image analysis for the assessment of the void fraction of the conductors withScanning Electron Microscopy (SEM) and energy dispersive X-ray spectroscopy (EDS) to evaluate the quality of the contact between the strands and the sleeve / sole of the joints

Characterization of low temperature high voltage axial insulator breaks for the ITER cryogenic supply line

Cable-in-conduit conductors of the ITER magnet system are directly cooled by supercritical helium. Insulation breaks are required in the liquid helium feed pipes to isolate the high voltage system of the magnet windings from the electrically grounded helium coolant supply line. They are submitted to high voltages and significant internal helium pressure and will experience mechanical forces resulting from differential thermal contraction and electro-mechanical loads. Insulation breaks consist essentially of stainless steel tubes overwrapped by an outer glass – fiber reinforced composite and bonded to an inner composite tube at each end of the stainless steel fittings. For some types of insulator breaks Glass – Kapton – Glass insulation layers are interleaved in the outer composite. Following an extensive mechanical testing campaign at cryogenic temperature combined with leak tightness tests, the present paper investigates through non-destructive and destructive techniques the physical and microstructural characteristics of the low temperature high voltage insulation breaks and of their individual components, thus allowing to correlate the structure and properties of the constituents to their overall performance. For all the tests performed, consistent and reproducible results were obtained within the range of the strict acceptance criteria defined for safe operation of the insulation breaks

Fatigue performance evaluation for ITER IVC conductor component materials

The ITER IVCs are made of stainless steel mineral-insulated conductors composed by an OFE copper conductor and a SS316LN jacket. The baseline design requires the coils to endure all ITER machine life time. After a brief review of past and recent literatures, no results are available and of our interest. Moreover, cold working, aging treatments as well as the environment temperature affect the mechanical and fatigue properties. The present paper summarizes data from tensile and uniaxial tension load controlled fatigue tests on both the steel jacket and the copper conductor in the IVC representative operation conditions. Tests are performed on specimens sectioned from the tubes undergone cold working of conductor compaction, coil winding and so on as well as heat treatment at 240 °C for 24 h of baking, and finally tested at operation temperature of 120 °C. The fatigue tests were conducted at frequency of 15 Hz and the stress ratio of R = 0.1. Results from tensile tests show both strength and ductility decrease as temperature rises from RT to 120 °C. Results from fatigue tests are presented as S-N relationships with the maximum stress expressed as a percentage of the strength under static loading. It was found that the fatigue strength limit for OFE copper conductor and SS316LN jacket were close to 120 MPa and 275 MPa respectively. The influence from residual stresses on the static and fatigue performance of 316LN jacket were also investigated It was found that the ductility and fatigue life can be improved by residual stress releasing of heat treatment at 650 °C for 100 h

Differentially Expressed Genes and Signaling Pathways Potentially Involved in Primary Resistance to Chemo-Immunotherapy in Advanced-Stage Gastric Cancer Patients

Recently, the combination of chemotherapy plus nivolumab (chemo-immunotherapy) has become the standard of care for advanced-stage gastric cancer (GC) patients. However, despite its efficacy, up to 40% of patients do not respond to these treatments. Our study sought to identify variations in gene expression associated with primary resistance to chemo-immunotherapy. Diagnostic endoscopic biopsies were retrospectively obtained from advanced GC patients previously categorized as responders (R) or non-responders (NR). Thirty-four tumor biopsies (R: n = 16, NR: n = 18) were analyzed by 3′ massive analysis of cDNA ends (3′MACE). We found >30 differentially expressed genes between R and NRs. Subsequent pathway enrichment analyses demonstrated that angiogenesis and the Wnt-β-catenin signaling pathway were enriched in NRs. Concomitantly, we performed next generation sequencing (NGS) analyses in a subset of four NR patients that confirmed alterations in genes that belonged to the Wnt/β-catenin and the phosphoinositide 3-kinase (PI3K) pathways. We speculate that angiogenesis, the Wnt, and the PI3K pathways might offer actionable targets. We also discuss therapeutic alternatives for chemo-immunotherapy-resistant advanced-stage GC patients

Guideline for the surgical treatment of atrial fibrillation.

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and its prevalence is approximately 1-2% of the general population, but higher with increasing age and in patients with concomitant heart disease. The Cox-maze III procedure was a groundbreaking development and remains the surgical intervention with the highest cure rate, but due to its technical difficulty alternative techniques have been developed to create the lesions sets. The field is fast moving and there are now multiple energy sources, multiple potential lesion sets and even multiple guidelines addressing the issues surrounding the surgical treatment of AF both for patients undergoing this concomitantly with other cardiac surgical procedures and also as stand-alone procedures either via sternotomy or via videothoracoscopic techniques. The aim of this document is to bring together all major guidelines in this area into one resource for clinicians interested in surgery for AF. Where we felt that guidance was lacking, we also reviewed the evidence and provided summaries in those areas. We conclude that AF surgery is an effective intervention for patients with all types of AF undergoing concomitant cardiac surgery to reduce the incidence of AF, as demonstrated in multiple randomized studies. There is some evidence that this translates into reduced stroke risk, reduced heart failure risk and longer survival. In addition, symptomatic patients with AF may be considered for surgery after failed catheter intervention or even as an alternative to catheter intervention where either catheter ablation is contraindicated or by patient choice