A time-varying inertia pendulum: Analytical modelling and experimental identification

In this paper two of the main sources of non-stationary dynamics, namely the time-variability and the presence of nonlinearity, are analysed through the analytical and experimental study of a time-varying inertia pendulum. The pendulum undergoes large swinging amplitudes, so that its equation of motion is definitely nonlinear, and hence becomes a nonlinear time-varying system. The analysis is carried out through two subspace-based techniques for the identification of both the linear time-varying system and the nonlinear system. The flexural and the nonlinear swinging motions of the pendulum are uncoupled and are considered separately: for each of them an analytical model is built for comparisons and the identification procedures are developed. The results demonstrate that a good agreement between the predicted and the identified frequencies can be achieved, for both the considered motions. In particular, the estimates of the swinging frequency are very accurate for the entire domain of possible configurations, in terms of swinging amplitude and mass positio

Effectiveness of an intervention to facilitate prompt referral to memory clinics in the United Kingdom: Cluster randomised controlled trial

Background Most people with dementia do not receive timely diagnosis, preventing them from making informed plans about their future and accessing services. Many countries have a policy to increase timely diagnosis, but trials aimed at changing general practitioner (GP) practice have been unsuccessful. We aimed to assess whether a GP’s personal letter, with an evidence-based leaflet about overcoming barriers to accessing help for memory problems—aimed at empowering patients and families—increases timely dementia diagnosis and patient presentation to general practice. Methods and finding Multicentre, cluster-randomised controlled trial with raters masked to an online computer-generated randomisation system assessing 1 y outcome. We recruited 22 general practices (August 2013–September 2014) and 13 corresponding secondary care memory services in London, Hertfordshire, and Essex, United Kingdom. Eligible patients were aged ≥70 y, without a known diagnosis of dementia, living in their own homes. There were 6,387 such patients in 11 intervention practices and 8,171 in the control practices. The primary outcome was cognitive severity on Mini Mental State Examination (MMSE). Main secondary outcomes were proportion of patients consulting their GP with suspected memory disorders and proportion of those referred to memory clinics. There was no between-group difference in cognitive severity at diagnosis (99 intervention, mean MMSE = 22.04, 95% confidence intervals (CIs) = 20.95 to 23.13; 124 control, mean MMSE = 22.59, 95% CI = 21.58 to 23.6; p = 0.48). GP consultations with patients with suspected memory disorders increased in intervention versus control group (odds ratio = 1.41; 95% CI = 1.28, 1.54). There was no between-group difference in the proportions of patients referred to memory clinics (166, 2.5%; 220, 2.7%; p = .077 respectively). The study was limited as we do not know whether the additional patients presenting to GPs had objective as well as subjective memory problems and therefore should have been referred. In addition, we aimed to empower patients but did not do anything to change GP practice. Conclusions Our intervention to access timely dementia diagnosis resulted in more patients presenting to GPs with memory problems, but no diagnoses increase. We are uncertain as to the reason for this and do not know whether empowering the public and targeting GPs would have resulted in a successful intervention. Future interventions should be targeted at both patients and GPs. Trial registration Current Controlled Trials ISRCTN1921687

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Practical Recommendations for the Diagnosis and Medical Management of Stable Angina: An Expert Panel Consensus

Stable angina affects a significant number of coronary artery disease patients, impairing their quality of life and worsening their prognosis. It manifests even despite a history of revascularization and is often poorly controlled with drug therapy. Comorbid conditions are frequently encountered in coronary artery disease patients, affecting their prognosis and rendering the diagnosis and management of angina more challenging. In this article, derived by an expert panel meeting, we attempt a practical approach to stable angina, focusing on symptomatic patients subjected to previous coronary revascularization or not suitable for revascularization and providing handy diagnostic and therapeutic algorithms and comorbidity-adjusted therapeutic approaches in accordance with existing evidence, current recommendations, and locally available therapeutic options. © 2020 Institute of Electrical and Electronics Engineers Inc.. All rights reserved

Practical Recommendations for the Diagnosis and Medical Management of Stable Angina: An Expert Panel Consensus

Stable angina affects a significant number of coronary artery disease patients, impairing their quality of life and worsening their prognosis. It manifests even despite a history of revascularization and is often poorly controlled with drug therapy. Comorbid conditions are frequently encountered in coronary artery disease patients, affecting their prognosis and rendering the diagnosis and management of angina more challenging. In this article, derived by an expert panel meeting, we attempt a practical approach to stable angina, focusing on symptomatic patients subjected to previous coronary revascularization or not suitable for revascularization and providing handy diagnostic and therapeutic algorithms and comorbidity-adjusted therapeutic approaches in accordance with existing evidence, current recommendations, and locally available therapeutic options. © 2020 Institute of Electrical and Electronics Engineers Inc.. All rights reserved