Explore the vast range of titles available.

There are several programmes within the fusion community that are engaged in the design of fusion devices to follow the International Thermonuclear Experimental Reactor (ITER), referred to as ‘demonstrators’. These programmes have identified many issues over the past decade, and research now concentrates on optimizing the combination of systems against a set of Key Performance Indicators (KPI) which may vary between programmes. While the return on investment in and experience from ITER is seen as an important factor in this research there are significant differences in the operational conditions and KPI of demonstrators that generate additional problems requiring different solutions. Among these problems are the necessary use of uncommon materials for structural and functional purposes, the impact of the availability KPI on basic machine design, configuration and component lifetime and the integration of the tritium fuel and thermodynamic cycles. These raise issues of component manufacture and standards and of resource availability in the required quantities and quality that are independent of device size and design. Interpreting ‘accelerating fusion’ in a wider sense, the impact of these issues, analysed in respect of developmental timescales, shows that a strategy of early engagement with the industrial supply chain and the development of computational engineering testing and verification will be essential to prevent prolonged timescales to fusion progress. This article is part of a discussion meeting issue ‘Fusion energy using tokamaks: can development be accelerated?’

In two randomized trials, two different doses of the oral gonadotropin-releasing hormone antagonist elagolix significantly reduced endometriosis-related dysmenorrhea and nonmenstrual pelvic pain but had hypoestrogenic adverse effects.

There are several programmes within the fusion community that are engaged in the design of fusion devices to follow the International Thermonuclear Experimental Reactor (ITER), referred to as ‘demonstrators’. These programmes have identified many issues over the past decade, and research now concentrates on optimizing the combination of systems against a set of Key Performance Indicators (KPI) which may vary between programmes. While the return on investment in and experience from ITER is seen as an important factor in this research there are significant differences in the operational conditions and KPI of demonstrators that generate additional problems requiring different solutions. Among these problems are the necessary use of uncommon materials for structural and functional purposes, the impact of the availability KPI on basic machine design, configuration and component lifetime and the integration of the tritium fuel and thermodynamic cycles. These raise issues of component manufacture and standards and of resource availability in the required quantities and quality that are independent of device size and design. Interpreting ‘accelerating fusion’ in a wider sense, the impact of these issues, analysed in respect of developmental timescales, shows that a strategy of early engagement with the industrial supply chain and the development of computational engineering testing and verification will be essential to prevent prolonged timescales to fusion progress. This article is part of a discussion meeting issue ‘Fusion energy using tokamaks: can development be accelerated?’

A summary of negative ion development work being presently undertaken at the Culham Centre for Fusion Energy is given. The small negative ion facility has an RF driven volume ion source with beam extraction at energies up to 30 keV. The extracted beam of H− ions has an associated co-extracted electron beam with an electron to ion ratio of <1 over the whole range of operating parameters. In order to understand this performance spectroscopic investigations have been undertaken using the Balmer series line to determine the electron temperature. In addition a 1D fluid model of an RF driven ion source is also under development. This model is based on a successful model for both arc discharge positive and negative ion sources. Additional system studies of neutral beam injection systems for future fusion machines beyond ITER are being carried out. This is required to understand the limits of various neutralisation and energy recovery systems in order to maximise overall electrical efficiency.

The analytic expression for the nonlinear magnetic susceptibility of a thin disk derived from Bean's model with a uniform JC for B∥n^ predicts a peak-peak ratio of 7.1 (5.4) for the real (imaginary) components of the third harmonic χ3 susceptibility. Our measurements show a peak-peak ratio closer to 1.1 in the real component and a noise limited lower estimate of ≈ 7 in the imaginary component. The anomalous third harmonic can be explained by the presence of a geometrical surface barrier for flux entry and exit which we have included as a small region of enhanced current density, JC,G, close to the surface of the disk. The geometrical surface current density is predicted to be approximately equal to JC,G ≈ 2BC1/μ0d. In 2G HTS tapes with d ≈ 1μm and BC1 ≈ 5mT this is JC,G ≈ 8GAm−2. We have measured both JC,B and JC,G using the nonlinear susceptibility of a Superpower tape without artificial pinning in fields orthogonal to the tape up to 35T. We find a geometrical surface current of JC,G ≈ 10GAm−2 and an average critical current density JC which is in good agreement with transport measurements performed on material from the same reel of tape.

A scaling law for Jc in commercial Nb-Ti wire is proposed that describes its magnetic field, temperature and strain dependence. The scaling law is used to fit extensive measurements of the total strand critical current density, Jc,TS(B, T, ε), with the applied field orthogonal to the axis of the wire. We present critical current density, heat capacity and resistivity measurements to obtain Bc2*(θ), which shows clear angular anisotropy. At 4.2 K, the resistivity data show Bc2*(B∥J)−Bc2*(B⊥J)≈1T. We also discuss whether the fusion community should consider re-optimising standard commercial Nb-Ti wires that were developed for MRI applications at ~ 5 T, to produce higher Jc at say 10T, and higher upper critical fields, perhaps using quaternary Nb-Ti alloys with artificial pinning centres.

Background Elagolix is an oral, gonadotropin-releasing hormone (GnRH) receptor antagonist, that significantly reduces dysmenorrhea and non-menstrual pelvic pain (NMPP) in women with moderate to severe endometriosis-associated pain. Methods Data were pooled from two 6-month, placebo-controlled, phase 3 studies (Elaris Endometriosis [EM]-I and II) in which 2 doses of elagolix were evaluated (150 mg once daily and 200 mg twice daily). Pooled data from > 1600 women, aged 18–49, were used to evaluate the efficacy of elagolix and health-related quality of life (HRQoL) in prespecified subgroups of women with various baseline characteristics. Results Of the 1686 women treated, 1285 (76.2%) completed the studies. The percentages of women with clinically meaningful reductions in dysmenorrhea and NMPP were generally consistent by subgroup. Significant treatment by subgroup interaction was demonstrated for dysmenorrhea response in baseline analgesic use ( p  < 0.01) and previous history of pregnancy ( p  < 0.05) subgroups, and for NMPP response in the baseline NMPP score ( p  < 0.05) and history of pregnancy ( p  < 0.05) subgroups. Patient-reported reduction in pain at month 3 was significant across all subgroups taking elagolix 200 mg BID, and significant across most subgroups with elagolix 150 mg QD. Women across subgroups experienced improvement within each domain of the Endometriosis Health Profile-30 (EHP-30), although significant treatment by subgroup interactions were observed in several categories. Conclusions Elagolix was effective in reducing dysmenorrhea and NMPP, and improving HRQoL, compared with placebo across numerous subgroups of women with various baseline characteristics, covering a broad segment of the endometriosis disease and patient types. Clinical trial registration : ClinicalTrials.gov: https://www.clinicaltrials.gov/ct2/show/NCT01620528 ; https://www.clinicaltrials.gov/ct2/show/NCT01931670 .

In this post hoc analysis, we evaluated the impact of elagolix on dysmenorrhea and nonmenstrual pelvic pain across menstrual period (bleeding days) and nonmenstrual (nonbleeding) days. Data from two randomized, 6-month, placebo-controlled trials (Elaris Endometriosis (EM)-I and EM-II) of elagolix (150 mg once daily (QD) and 200 mg twice daily (BID)) in premenopausal women with moderate to severe endometriosis-associated pain (N = 1686) were pooled. Women recorded the presence of menstrual period and severity of dysmenorrhea or nonmenstrual pelvic pain in a daily electronic diary. At baseline, women in the placebo group and both elagolix treatment groups reported moderate or severe dysmenorrhea, on average, 81% of their menstrual period days and moderate/severe nonmenstrual pelvic pain, on average, 56% of their nonmenstrual (nonbleeding) days. Compared with placebo at month 6, elagolix-treated women had a significantly lower mean (standard deviation (SD)) percentage of menstrual period days with moderate or severe dysmenorrhea (elagolix 150 mg QD = 52.4 (38.9), p = 0.002; elagolix 200 mg BID = 38.5 (43.6), p < 0.001, placebo = 61.3 (33.7)) and a significantly lower mean (SD) percentage of nonmenstrual (nonbleeding) days with moderate or severe nonmenstrual pelvic pain (elagolix 150 mg QD = 31.1 (35.8), p < 0.001; elagolix 200 mg BID = 19.7 (29.9), p < 0.001; placebo = 35.6 (33.9)). Following 6 months of elagolix treatment, women who still menstruated had a lower proportion of menstrual period days with moderate or severe dysmenorrhea compared with placebo, demonstrating pain reduction despite continued menses. Additionally, pain did not shift from dysmenorrhea to nonmenstrual pelvic pain, as the percentage of days with moderate or severe nonmenstrual pelvic pain was also reduced for elagolix-treated women compared with placebo. The Elaris EM-I study is registered with the US National Library of Medicine, www.ClinicalTrials.gov, NCT01620528. The Elaris EM-II study is registered with the US National Library of Medicine, www.ClinicalTrials.gov, NCT01931670. Both studies are registered with the EU Clinical Trial Register, www.clinicaltrialsregister.ed, 2011-004295-11.

Background Endometriosis is a common problem in women of reproductive age and has impacts on health-related quality of life and productivity. Fatigue is an important part of the burden of endometriosis, it is not often included as an endpoint in clinical trials. Objectives The study assessed the psychometric properties of the PROMIS Fatigue Short Form 6a in women with moderate-to-severe endometriosis-associated pain. Methods In a phase III double-blind, placebo-controlled clinical trial (NCT01620528), women aged 18–49 years with moderate-to-severe endometriosis-related pain were randomized to elagolix 150 mg once daily, elagolix 200 mg twice daily, or placebo for 6 months. PROMIS Fatigue and dysmenorrhea and non-menstrual pelvic pain (NMPP) scores were assessed at baseline and months 1, 3, and 6, and Patient Global Impression of Change (PGIC) was assessed at months 1, 3, and 6. Reliability (internal consistency and test-retest reliability), construct validity (convergent and known groups validity), and responsiveness were evaluated. Results The analysis included 871 women, mean age 31.5 years. Internal consistency supported a single concept (Cronbach’s alpha 0.93). For the 238 patients with no change in PGIC at month 1, the intraclass correlation coefficient for the PROMIS Fatigue T-score was 0.7 and paired t-test statistically significant (2.84, p  = 0.0049). Correlations with other measures were expected to be fairly low as concepts were not redundant. The PROMIS Fatigue discriminated among known groups with mean scores of 55.3, 62.3, and 65.8 at month 3 (PGIC improvement, no change, worsening, respectively). Statically significant discrimination, and change score responsiveness, were seen using clinically relevant anchors (dysmenorrhea and NMPP) at months 3 and 6 between responders and non-responders. Anchor-based (PGIC) responsiveness showed significant improvement from baseline to months 3 and 6 ( p  < 0.0001). Conclusions PROMIS Fatigue has good reliability, validity, and responsiveness in women with moderate-to-severe endometriosis-associated pain.