Neutron Position Sensitive Detectors for the ESS

The European Spallation Source (ESS) in Lund, Sweden will become the world's leading neutron source for the study of materials. The instruments are being selected from conceptual proposals submitted by groups from around Europe. These instruments present numerous challenges for detector technology in the absence of the availability of Helium-3, which is the default choice for detectors for instruments built until today and due to the extreme rates expected across the ESS instrument suite. Additionally a new generation of source requires a new generation of detector technologies to fully exploit the opportunities that this source provides. The detectors will be sourced from partners across Europe through numerous in-kind arrangements; a process that is somewhat novel for the neutron scattering community. This contribution presents briefly the current status of detectors for the ESS, and outlines the timeline to completion. For a conjectured instrument suite based upon instruments recommended for construction, a recently updated snapshot of the current expected detector requirements is presented. A strategy outline as to how these requirements might be tackled by novel detector developments is shown. In terms of future developments for the neutron community, synergies should be sought with other disciples, as recognized by various recent initiatives in Europe, in the context of the fundamentally multi-disciplinary nature of detectors. This strategy has at its basis the in-kind and collaborative partnerships necessary to be able to produce optimally performant detectors that allow the ESS instruments to be world-leading. This foresees and encourages a high level of collaboration and interdependence at its core, and rather than each group being all-rounders in every technology, the further development of centres of excellence across Europe for particular technologies and niches.Comment: 8 pages, 1 figure. Proceedings from the 23rd International Workshop on Vertex Detectors, 15-19 September 2014, Macha Lake, The Czech Republic. PoS(Vertex2014)02

3 years of liraglutide versus placebo for type 2 diabetes risk reduction and weight management in individuals with prediabetes: a randomised, double-blind trial

Background: Liraglutide 3·0 mg was shown to reduce bodyweight and improve glucose metabolism after the 56-week period of this trial, one of four trials in the SCALE programme. In the 3-year assessment of the SCALE Obesity and Prediabetes trial we aimed to evaluate the proportion of individuals with prediabetes who were diagnosed with type 2 diabetes. Methods: In this randomised, double-blind, placebo-controlled trial, adults with prediabetes and a body-mass index of at least 30 kg/m2, or at least 27 kg/m2 with comorbidities, were randomised 2:1, using a telephone or web-based system, to once-daily subcutaneous liraglutide 3·0 mg or matched placebo, as an adjunct to a reduced-calorie diet and increased physical activity. Time to diabetes onset by 160 weeks was the primary outcome, evaluated in all randomised treated individuals with at least one post-baseline assessment. The trial was conducted at 191 clinical research sites in 27 countries and is registered with ClinicalTrials.gov, number NCT01272219. Findings: The study ran between June 1, 2011, and March 2, 2015. We randomly assigned 2254 patients to receive liraglutide (n=1505) or placebo (n=749). 1128 (50%) participants completed the study up to week 160, after withdrawal of 714 (47%) participants in the liraglutide group and 412 (55%) participants in the placebo group. By week 160, 26 (2%) of 1472 individuals in the liraglutide group versus 46 (6%) of 738 in the placebo group were diagnosed with diabetes while on treatment. The mean time from randomisation to diagnosis was 99 (SD 47) weeks for the 26 individuals in the liraglutide group versus 87 (47) weeks for the 46 individuals in the placebo group. Taking the different diagnosis frequencies between the treatment groups into account, the time to onset of diabetes over 160 weeks among all randomised individuals was 2·7 times longer with liraglutide than with placebo (95% CI 1·9 to 3·9, p<0·0001), corresponding with a hazard ratio of 0·21 (95% CI 0·13–0·34). Liraglutide induced greater weight loss than placebo at week 160 (–6·1 [SD 7·3] vs −1·9% [6·3]; estimated treatment difference −4·3%, 95% CI −4·9 to −3·7, p<0·0001). Serious adverse events were reported by 227 (15%) of 1501 randomised treated individuals in the liraglutide group versus 96 (13%) of 747 individuals in the placebo group. Interpretation: In this trial, we provide results for 3 years of treatment, with the limitation that withdrawn individuals were not followed up after discontinuation. Liraglutide 3·0 mg might provide health benefits in terms of reduced risk of diabetes in individuals with obesity and prediabetes. Funding: Novo Nordisk, Denmark

Immunogenicity and safety of a quadrivalent meningococcal tetanus toxoid-conjugate vaccine (MenACYW-TT) in adults 56 years of age and older: a Phase II randomized study

MenACYW-TT is an investigational quadrivalent meningococcal conjugate vaccine intended for the prevention of invasive meningococcal disease (IMD) caused by serogroups A, C, W, and Y in individuals aged 6 weeks and above. This Phase II, randomized, open-label, multicenter, exploratory study assessed the safety and immunogenicity of MenACYW-TT compared with a quadrivalent meningococcal polysaccharide vaccine (MPSV4) in 301 healthy adults aged ≥56 y in the US (NCT01732627). Participants were randomized 2:1 to receive MenACYW-TT or MPSV4. Serum bactericidal assays using human (hSBA) or baby rabbit (rSBA) complement were used to measure functional antibodies against meningococcal serogroups A, C, W, and Y at baseline and 30 d post-vaccination. Safety data were collected up to 30 d post-vaccination. Proportions of study participants with hSBA titers ≥1:8 against serogroups A, C, W, and Y were increased at Day 30 compared with baseline in both vaccine groups. The proportions of participants with hSBA titers ≥1:8 after MenACYW-TT vaccination were comparable to those after MPSV4 vaccination for serogroups A and C (A: 93.8% vs. 85.1%; C: 74.9% vs. 62.8%) and distinctly higher than after MPSV4 for serogroups W and Y (W: 79.5% vs. 60.6%; Y: 80.5% vs. 59.6%). Proportions of participants with rSBA titers ≥1:8 were comparable between vaccine groups for all four serogroups. The reactogenicity profiles of both vaccines were similar. Most unsolicited adverse events (AEs) were of Grade 1 or Grade 2 intensity, and no serious AEs were reported. The MenACYW-TT conjugate vaccine was well tolerated and immunogenic in adults aged ≥56 y

Immunogenicity of the CYD tetravalent dengue vaccine using an accelerated schedule: randomised phase II study in US adults

Abstract Background The live attenuated tetravalent dengue vaccine (CYD-TDV) is licensed using a 0-, 6- and 12-month schedule in dengue-endemic areas. An effective shorter schedule may provide more rapid, optimal protection of targeted populations during vaccine campaigns in dengue-endemic countries. We compared immune responses to two schedules of CYD-TDV in a non-endemic population. We also evaluated the impact of yellow fever (YF) co-administration. Methods This phase II, open-label, multicentre study enrolled 390 healthy 18–45-year-olds in the USA with no prior exposure to dengue. Participants were randomised (4:4:4:1) to four treatment groups stratified by prior YF vaccine status: Group 1, CYD-TDV standard 0–6–12 months schedule; Group 2, CYD-TDV accelerated 0–2–6 months schedule; Group 3, CYD-TDV accelerated schedule with YF co-administered (dose 1); Group 4, YF vaccination only. Neutralising antibody geometric mean titres (GMTs) and percentages of seropositive participants (antibody titres ≥10 [1/dil]) were measured against each dengue serotype using a 50% plaque reduction neutralisation test. Results On D28 post-CYD-TDV dose 3, there were no marked differences in seropositivity rates and GMTs between Groups 1 and 2. In Groups 1 and 2 respectively, 73.4 and 82.4% were dengue seropositive for ≥3 serotypes, with 50.0 and 42.6% seropositive against all four serotypes. Flavivirus status (FV+ or FV−) at baseline did not markedly affect GMTs and seropositivity rates with either schedule. In Groups 1 and 2, GMTs measured 6 months after the third dose decreased against all serotypes, except for a small increase in GMT for serotype 4 in Group 1. In addition, dengue seropositivity remained above 70% for serotypes 2, 3 and 4 in Groups 1 and 2. Co-administration with YF did not affect antibody responses against dengue and YF or impact vaccine safety following completion of the compressed schedule, compared to dengue or YF vaccination alone. Conclusions The live attenuated CYD-TDV vaccine given in a compressed schedule in a non-endemic setting can elicit similar antibody responses to the licensed CYD-TDV schedule. Trial registration This trial was registered on cinicaltrials.gov, NCT01488890 (December 8, 2011)

Comparison of mammographic changes across three different fractionation schedules for early-stage breast cancer

© 2016 Elsevier Inc. All rights reserved. Purpose As the use of hypofractionated breast radiation therapy (RT) increases, so will the need for long-term data on post-RT mammographic changes. The purpose of the present study was to longitudinally compare the incidence of common mammographic sequelae seen after breast conserving surgery and RT in patients treated with accelerated partial breast irradiation (APBI), hypofractionated whole breast irradiation (HWBI), and conventionally fractionated whole breast irradiation (WBI). Methods and Materials Patients treated with either APBI or HWBI after breast conserving therapy and with ≥3 mammograms of the treated breast were identified. They were matched 1:1 by age ±5 years to patients treated with WBI. The mammograms were evaluated for common post-RT breast findings by a mammographer who was unaware of the treatment. The outcomes were analyzed using a cumulative logistic regression model; P\u3c.05 indicated statistically significance. Results Of 89 patients treated with RT from 2006 to 2011, 29 had received APBI, 30 had received HWBI, and 30 had received WBI. Their median age was 60 years (range 33-83). A total of 605 mammograms were evaluated, with a median follow-up of 48 months. The treatment technique did not affect the severity of architectural distortion when the groups were evaluated longitudinally. The likelihood of finding skin thickening decreased with increasing follow-up duration (odds ratio 0.6; P\u3c.001) adjusted for fractionation schemes. No differences were seen with respect to changes in skin thickening, fluid collections, or calcifications among the treatment groups, after adjustment for the follow-up time. The clinical characteristics, including age, race, T stage, and chemotherapy use, were not linked to the likelihood of finding several mammographic phenomena over time. Conclusions Although specific post-treatment imaging findings evolved over time, RT fractionation did not alter the relative incidence or severity of architectural distortion, skin thickening, fluid collections, or calcifications. These findings will be useful to both radiologists and radiation oncologists when counseling patients regarding follow-up studies after RT

Effect of concomitant Renal DeNervation and cardiac ablation on Atrial Fibrillation recurrence: RDN+AF study

Background: Renal denervation (RDN) can reduce cardiac sympathetic activity maintained by arterial hypertension (aHT). Its potential antiarrhythmic effect on rhythm outcome in patients with multi-drug resistant aHT undergoing catheter ablation for atrial fibrillation (AF) is unclear. Methods: The RDN+AF study was a prospective, randomized, two-center trial. Patients with paroxysmal or persistent AF and uncontrolled aHT (mean systolic 24-h ambulatory BP > 135 mmHg) despite taking at least three antihypertensive drugs were enrolled. Patients were 1:2 randomized to either RDN+AF ablation or AF-only ablation. Primary endpoint was freedom from any AF episode > 2 min at 12 months assessed by implantable loop recorder (ILR) or 7d-holter electrocardiogram. Secondary endpoints included rhythm outcome at 24 months, blood pressure control, periprocedural complications, and renovascular safety. Results: The study randomized 61 patients (mean age 65 ± 9 years, 53% men). At 12 months, RDN+AF patients tended to have a greater decrease in ambulatory BPs but did not reach statistical significance. No differences in rhythm outcome were observed. Freedom from AF recurrence in the RDN+AF and AF-only group measured 61% versus 53% p = .622 at 12 months and 39% versus 47% p = .927 at 24 months, respectively. Periprocedural complications occurred in 9/61 patients (15%). No patient died. Conclusion: Among patients with multidrug-resistant aHT and paroxysmal or persistent AF, concomitant RDN+AF ablation was not associated with better blood pressure control or rhythm outcome in comparison to AF-only ablation and medical therapy