Design, construction, and quality tests of the large Al-alloy mandrels for the CMS coil

The Compact Muon Solenoid (CMS) is one of the general-purpose detectors to be provided for the LHC project at CERN. The design field of the CMS superconducting magnet is 4 T, the magnetic length is 12.5 m and the free bore is 6 m. Almost all large indirectly cooled solenoids constructed to date (e.g., Zeus, Aleph, Delphi, Finuda, Babar) comprise Al-alloy mandrels fabricated by welding together plates bent to the correct radius. The external cylinder of CMS will consist of five modules having an inner diameter of 6.8 m, a thickness of 50 mm and an individual length of 2.5 m. It will be manufactured by bending and welding thick plates (75 mm) of the strain hardened aluminum alloy EN AW-5083-H321. The required high geometrical tolerances and mechanical strength (a yield strength of 209 MPa at 4.2 K) impose a critical appraisal of the design, the fabrication techniques, the welding procedures and the quality controls. The thick flanges at both ends of each module will be fabricated as seamless rolled rings, circumferentially welded to the body of the modules. The developed procedures and manufacturing methods will be validated by the construction of a prototype mandrel of full diameter and reduced length (670 mm). (7 refs)

Glycopyrrolate/formoterol fumarate metered dose inhaler for maintenance-naïve patients with chronic obstructive pulmonary disease:a post-hoc analysis of the randomized PINNACLE trials

Background: Glycopyrrolate (GP)/formoterol fumarate (FF; GFF) metered dose inhaler is a fixed-dose combination dual bronchodilator for patients with chronic obstructive pulmonary disease (COPD); however, whether the efficacy in patients without current maintenance treatment is consistent with currently maintenance-treated patients is unclear.Methods: Data from patients who were not maintenance-treated at screening (NMT) (n = 1943) and patients who were maintenance-treated at screening (MT) patients (n = 3040) receiving GFF, FF, GP, or placebo were pooled from the Phase III PINNACLE studies (NCT01854645, NCT01854658, NCT02343458) for post-hoc analysis. MT patients had received long-acting bronchodilators and/or inhaled corticosteroids in the 30 days prior to screening, and/or prior to randomization. NMT patients had received short-acting bronchodilators or no treatment. Outcomes included forced expiratory volume over 1 s (FEV1), clinically important deterioration (CID), rescue medication use, and safety.Results: GFF provided significant lung function improvements at Week 24 versus placebo, GP, and FF for NMT patients, with pre-dose trough FEV1 treatment differences of 152 (117-188) mL, 73 (45-100) mL, and 56 (29-84) mL, respectively (least squares mean change from baseline versus comparators [95% CI]; all P &lt; 0.0001). GFF reduced the risk of CID by 17-43% in NMT (P ≤ 0.0157) and 18-52% (P ≤ 0.0012) in MT patients compared with monotherapy and placebo, and reduced rescue medication use by 1.5 puffs/day over 24 weeks for both cohorts. Safety profiles for all cohorts were consistent with each other and the parent studies.Conclusions: NMT patients achieved better lung function with GFF versus monotherapy and placebo, without increased safety risk. Dual bronchodilator therapy may offer better outcomes than monotherapy for COPD patients when administered as first-line treatment.</p

“Design is one”, un canone grafico del progetto di social design; 10 anni di ricerca-azione

Ragioneremo attorno alla nostra esperienza progettuale, consapevoli che esiste un aspetto comunicativo in ogni progetto e concordi che indagare e interrogare questa dimensione permetta di comprendere e definire “meglio le funzioni e scoprire altri tipi di funzionalità […] altrettanto essenziali che la pura considerazione funzionalistica impediva di scorgere”. Nel nostro lavoro di ricerca-azione partecipativa, infatti, funzione e comunicazione, prestazione e messaggio interagiscono nel corso di tutto il ciclo di vita del progetto

Metabolic Effects Associated with ICS in Patients with COPD and Comorbid Type 2 Diabetes: A Historical Matched Cohort Study

Background Management guidelines for chronic obstructive pulmonary disease (COPD) recommend that inhaled corticosteroids (ICS) are prescribed to patients with the most severe symptoms. However, these guidelines have not been widely implemented by physicians, leading to widespread use of ICS in patients with mild-to-moderate COPD. Of particular concern is the potential risk of worsening diabetic control associated with ICS use. Here we investigate whether ICS therapy in patients with COPD and comorbid type 2 diabetes mellitus (T2DM) has a negative impact on diabetic control, and whether these negative effects are dose-dependent. Methods and Findings This was a historical matched cohort study utilising primary care medical record data from two large UK databases. We selected patients aged >= 40 years with COPD and T2DM, prescribed ICS (n = 1360) or non-ICS therapy (n = 2642) between 2008 and 2012. The primary endpoint was change in HbA(1c) between the baseline and outcome periods. After 1:1 matching, each cohort consisted of 682 patients. Over the 12-18-month outcome period, patients prescribed ICS had significantly greater increases in HbA1c values compared with those prescribed non-ICS therapies; adjusted difference 0.16% (95% confidence interval [Cl]: 0.05-0.27%) in all COPD patients, and 0.25% (95% Cl: 0.10-0.40%) in mild-to-moderate COPD patients. Patients in the ICS cohort also had significantly more diabetes-related general practice visits per year and received more frequent glucose strip prescriptions, compared with those prescribed non-ICS therapies. Patients prescribed higher cumulative doses of ICS (> 250 mg) had greater odds of increased HbA(1c) and/or receiving additional antidiabetic medication, and increased odds of being above the Quality and Outcomes Framework (QOF) target for HbA1c levels, compared with those prescribed lower cumulative doses ( Conclusion For patients with COPD and comorbid T2DM, ICS therapy may have a negative impact on diabetes control. Patients prescribed higher cumulative doses of ICS may be at greater risk of diabetes progression

Prevalence and Characteristics of Asthma-COPD Overlap in Routine Primary Care Practices

Rationale: Adults may exhibit characteristics of both asthma and chronic obstructive pulmonary disease (COPD), a situation recently described as asthma-COPD overlap (ACO). There is a paucity of information about ACO in primary care. Objectives: To estimate the prevalence and describe characteristics of individuals withACOin primary care practices among patients currently diagnosed with asthma, COPD, or both; and to compare the prevalence and characteristics of ACO among the three source populations. Methods: The Respiratory Effectiveness Group conducted a crosssectional study of individuals ≥40 years old and with ≥2 outpatient primary care visits over a 2-year period in theUKOptimum Patient Care Research Database. Patients were classified into one of three source populations based on diagnostic codes: 1) COPD only, 2) both asthma and COPD, or 3) asthma only.ACOwas defined as the presence of all of the following 1) age ≥40 years, 2) current or former smoking, 3) postbronchodilator airflow limitation (forced expiratory volume in 1 second/ forced vital capacity <0.7), and 4) ≥12% and ≥200 ml reversibility in post-bronchodilator forced expiratory volume in 1 second. Results: Among 2,165 individuals (1,015 COPD only, 395 with both asthma and COPD, and 755 asthma only), the overall prevalence of ACO was 20% (95% confidence interval, 18-23%). Patients with ACO had a mean age of 70 years (standard deviation, 11 yr), 60% were men, 73% were former smokers (the rest were current smokers), and 66% were overweight or obese. Comorbid conditions were common in patients with ACO, including diabetes (53%), cardiovascular disease (36%), hypertension (30%), eczema (23%), and rhinitis (21%). The prevalence of ACO was higher in patients with a diagnosis of both asthma and COPD (32%) compared with a diagnosis of COPD only (20%; P<0.001) or asthma only (14%; P<0.001). Demographic and clinical characteristics of ACO varied across these three source populations. Conclusions: One in five individuals with a diagnosis of COPD, asthma, or both asthma and COPD in primary care settings have ACO based on the Respiratory Effectiveness Group ACO Working group criteria. The prevalence and characteristics of patients with ACO varies across the three source populations

Shelter Projects 2015-2016

Spanning humanitarian responses from all over the world, Shelter Projects 2015-2016 is the sixth in a series of compilations of shelter case studies, overviews of emergencies and opinion pieces. The projects represent responses to conflict, natural disasters and complex or multiple crises, demonstrating some of the implementation and response options available. The book is intended to support learning by highlighting the strengths, weaknesses and some of the lessons that can be learned from different projects, which try to maximize emergency funds to safeguard the health, security and dignity of affected people, whilst – wherever possible – supporting longer-term shelter needs and sustainable recovery. The target audience is humanitarian managers and shelter programme staff from local, national and international organizations at all levels of experience. Shelter Projects is also a useful resource for advocacy purposes, showcasing the work done by the sector, as well as for research and capacity-building activities

Improved adherence with once-daily versus twice-daily dosing of mometasone furoate administered via a dry powder inhaler: a randomized open-label study

Background Poor adherence with prescribed asthma medication is a major barrier to positive treatment outcomes. This study was designed to determine the effect of a once-daily administration of mometasone furoate administered via a dry powder inhaler (MF-DPI) on treatment adherence compared with a twice-daily administration. Methods This was a 12-week open-label study designed to mimic an actual clinical setting in patients ≥12 years old with mild-to-moderate persistent asthma. Patients were randomized to receive MF-DPI 400 μg once-daily in the evening or MF-DPI 200 μg twice-daily. Adherence was assessed primarily using the number of actual administered doses reported from the device counter divided by the number of scheduled doses. Self-reports were also used to determine adherence. Health-related quality of life, healthcare resource utilization, and days missed from work or school were also reported. Results 1233 patients were randomized. The mean adherence rates, as measured by the automatic dose counter, were significantly better (P < 0.001) with MF-DPI 400 μg once-daily in the evening (93.3%) than with MF-DPI 200 μg twice-daily (89.5%). Mean adherence rates based on self-reports were also significantly better (P < 0.001) with MF-DPI 400 μg QD PM (97.2%) than with MF-DPI 200 μg twice-daily (95.3%). Adherence rates were lower in adolescents (12-17 years old). Health-related quality of life improved by 20% in patients using MF-DPI once-daily in the evening and by 14% in patients using MF-DPI twice-daily. Very few (<8%) patients missed work/school. Conclusion Mean adherence rates were greater with a once-daily dosing regimen of MF-DPI than with a twice-daily dosing regimen. This trial was completed prior to the ISMJE requirements for trial registration

Research priorities to address the global burden of chronic obstructive pulmonary disease (COPD) in the next decade

Background The global prevalence of chronic obstructive pulmonary disease (COPD) has increased markedly in recent decades. Given the scarcity of resources available to address global health challenges and respiratory medicine being relatively under-invested in, it is important to define research priorities for COPD globally. In this paper, we aim to identify a ranked set of COPD research priorities that need to be addressed in the next 10 years to substantially reduce the global impact of COPD. Methods We adapted the Child Health and Nutrition Research Initiative (CHNRI) methodology to identify global COPD research priorities. Results 62 experts contributed 230 research ideas, which were scored by 34 researchers according to six pre-defined criteria: answerability, effectiveness, feasibility, deliverability, burden reduction, and equity. The top-ranked research priority was the need for new effective strategies to support smoking cessation. Of the top 20 overall research priorities, six were focused on feasible and cost-effective pulmonary rehabilitation delivery and access, particularly in primary/community care and low-resource settings. Three of the top 10 overall priorities called for research on improved screening and accurate diagnostic methods for COPD in low-resource primary care settings. Further ideas that drew support involved a better understanding of risk factors for COPD, development of effective training programmes for health workers and physicians in low resource settings, and evaluation of novel interventions to encourage physical activity. Conclusions The experts agreed that the most pressing feasible research questions to address in the next decade for COPD reduction were on prevention, diagnosis and rehabilitation of COPD, especially in low resource settings. The largest gains should be expected in low- and middle-income countries (LMIC) settings, as the large majority of COPD deaths occur in those settings. Research priorities identified by this systematic international process should inform and motivate policymakers, funders, and researchers to support and conduct research to reduce the global burden of COPD

Long-term outcomes of COVID-19 vaccination in patients with rare and complex connective tissue diseases: The ERN-ReCONNET VACCINATE study

Background: Vaccination is one of the most important measures to contain the COVID-19 pandemic, especially for frail patients. VACCINATE is a multicentre prospective observational study promoted by the European Reference Network on Rare and Complex Connective Tissue and Musculoskeletal Diseases (ERN ReCONNET) aimed at assessing the long-term outcomes of COVID-19 vaccination in patients with rare and complex connective tissue diseases (rcCTDs) in terms of efficacy and safety. Methods: Adult rcCTDs patients were eligible for recruitment. Demographic, clinical and vaccination data were collected at enrolment. Follow-up visits were scheduled 4, 12, 24, 36 and 48 weeks after completion of the first vaccination cycle; data on adverse events, disease exacerbations and the occurrence of new SARS-CoV-2 infections were collected at these time-points. Findings: 365 rcCTDs patients (87 % female, mean age 51.8 ± 14.6 years) were recruited. Overall, 200 patients (54.8 %) experienced at least one adverse event, generally mild and in most cases occurring early after the vaccination. During follow-up, 55 disease exacerbations were recorded in 39 patients (10.7 %), distributed over the entire observation period, although most frequently within 4 weeks after completion of the vaccination cycle. The incidence of new SARS-CoV-2 infections was 8.9 per 1000 person-months, with no cases within 12 weeks from vaccine administration and an increasing trend of infections moving away from the primary vaccination cycle. Only one case of severe COVID-19 was reported during the study period. Interpretation: COVID-19 vaccination seems effective and safe in rcCTDs patients. The rate of new infections was rather low and serious infections were uncommon in our cohort. No increased risk of disease flares was observed compared to previous disease history; however, such exacerbations may be potentially severe, emphasising the need for close monitoring of our patients