A robust line search for learning control

In this paper a new line search for a Newton Rhapson learning control algorithm is presented. Theorems and rigorous proofs of its increased robustness over existing line searches are provided, and numerical examples are used to further validate the theorems. Also, the previously posed open question of whether robust optimal trajectory learning is possible is also addressed. It is shown that the answer is generally no, at least for gradient-based learning control algorithms

Cost-effectiveness analysis of umeclidinium bromide/vilanterol 62.5/25 mcg versus tiotropium/olodaterol 5/5 mcg in symptomatic patients with chronic obstructive pulmonary disease: A Spanish National Healthcare System perspective

Background: A head-to-head study demonstrated the superiority of once-daily umeclidinium bromide/vilanterol (UMEC/VI) 62.5/25 mcg on trough forced expiratory volume in 1 s (FEV1) versus once-daily tiotropium/olodaterol (TIO/OLO) 5/5 mcg in symptomatic patients with chronic obstructive pulmonary disease (COPD). This analysis evaluated the cost effectiveness of UMEC/VI versus TIO/OLO from a Spanish National Healthcare System perspective, using data from this study and Spanish literature. Methods: This analysis was conducted from the perspective of the Spanish National Healthcare System with a 3-year horizon as base case. A disease progression model using a linked risk equation approach was used to estimate disease progression and associated healthcare costs, and quality-adjusted life years (QALYs). The Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study was used to develop the statistical risk equations for clinical endpoints, and costs were calculated using a health state approach (by dyspnea severity). Utilities for QALY calculation were estimated using patient baseline characteristics within a regression fit to Spanish observational data. Treatment effect, expressed as change from baseline in FEV1 was obtained from the head-to-head study and used in the model (UMEC/VI minus TIO/OLO difference: + 52 mL [95% confidence interval: 28, 77]). Baseline patient characteristics were sourced from Spanish literature or the head-to-head study if unavailable. A scenario analysis using only the intent-to-treat (ITT) population from the head-to-head study, and sensitivity analyses (including probabilistic sensitivity analyses), were conducted. Direct healthcare costs (2017 Euro) were obtained from Spanish sources and costs and benefits were discounted at 3% per annum. Results: UMEC/VI was associated with small improvements in QALYs (+ 0.029) over a 3-year time horizon, compared with TIO/OLO, alongside cost savings of €393/patient. The ITT scenario analysis and sensitivity analyses had similar results. All probabilistic simulations resulted in UMEC/VI being less costly and more effective than TIO/OLO. Conclusion: UMEC/VI dominated TIO/OLO (more effective and less expensive). These results may aid payers and decision-makers in Spain when making judgements on which long-acting muscarinic antagonist/long-acting β2-agonist (LAMA/LABA) treatments can be considered cost effective in Spain.This study was funded by GSK (study number HO-17-17500). The funders of the study had a role in study design, data analysis, data interpretation, and writing of the report. Data analysis was conducted by ICON Health Economics and funded by GSK. No funding was provided to employees of ICON Health Economics for manuscript developmen

Management of Patellar Chondral Defects with Autologous Matrix Induced Chondrogenesis (AMIC) Compared to Microfractures: A Four Years Follow-Up Clinical Trial.

INTRODUCTION: Evidence on the management of chondral defects of the patella arises from studies in which the patellofemoral joint was treated together with the femorotibial joint and primary and revision settings. Furthermore, the superiority of Autologous Matrix Induced Chondrogenesis (AMIC) over microfractures (MFx) for patellar chondral defects is uncertain. Therefore, the present study compared primary isolated AMIC versus MFx for focal unipolar chondral defects of the patellar facet joints at midterm follow-up. METHODS: Patients undergoing AMIC or isolated MFx surgery for borderline-sized focal unipolar chondral defects of the patellar facet joints were followed at our institution. All surgeries were performed in the same fashion by experienced surgeons. A parapatellar arthrotomy was adopted in all surgeries. The outcomes of interest were: Visual Analogic Scale (VAS), Tegner Activity Scale, International Knee Documentation Committee (IKDC), and the Lysholm scores. The Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) was assessed by a blinded radiologist, who had not been involved in the clinical management of the patients. RESULTS: 38 patients were enrolled in the present study: 27 underwent AMIC, and 11 MFx. The mean follow-up was 45.1 months. The mean age of the patients at baseline was 34.5 years. The mean size of the defect was 2.6 cm2. The MFx cohort experienced a shorter length of the hospitalization (P = 0.008). There was no difference in terms of follow-up and previous symptoms duration, mean age, sex, side, defect size, and BMI. At last follow-up, the AMIC cohort reported greater IKDC (P = 0.01), Lysholm (P = 0.009), and Tegner (P = 0.02), along with a low rate of failure (P = 0.02). VAS was lower in the AMIC group (P = 0.002). No difference was found in the MOCART score (P = 0.09), rates of revision (P = 0.06), and arthroplasty (P = 0.2). CONCLUSION: The AMIC procedure achieves greater IKDC and Lysholm score, and a significant reduction of the VAS score in the management of patellar chondral defects. The Tegner scale demonstrated greater activity after AMIC procedure. Finally, the AMIC group evidenced a lower rate of failure. Similarity was found on MOCART score, rates of revision, and arthroplasty between the two procedures

Autologous Matrix Induced Chondrogenesis (AMIC) Compared to Microfractures for Chondral Defects of the Talar Shoulder: A Five-Year Follow-Up Prospective Cohort Study.

INTRODUCTION: Many procedures are available to manage cartilage defects of the talus, including microfracturing (MFx) and Autologous Matrix Induced Chondrogenesis (AMIC). Whether AMIC or MFx are equivalent for borderline sized defects of the talar shoulder is unclear. Thus, the present study compared the efficacy of primary isolated AMIC versus MFx for borderline sized focal unipolar chondral defects of the talar shoulder at midterm follow-up. METHODS: Patients undergoing primary isolated AMIC or MFx for focal unipolar borderline sized chondral defects of the talar shoulder were recruited prospectively. For those patients who underwent AMIC, a type I/III collagen resorbable membrane was used. The outcomes of interest were: Visual Analogic Scale (VAS), Tegner Activity Scale, American Orthopedic Foot and Ankle Score (AOFAS). The Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) was assessed by a blinded radiologist, who had not been involved in the clinical management of the patients. Data concerning complication rate and additional procedures were also collected. RESULTS: The mean follow-up was 43.5 months. The mean age of the 70 patients at operation was 32.0 years, with a mean defect size of 2.7 cm2. The mean length of hospitalization was shorter in the MFx cohort (p = 0.01). No difference was found between the two cohorts in terms of length of prior surgery symptoms and follow-up, mean age and BMI, sex and side, and defect size. At a mean follow-up of 43.5 months, the AOFAS (p = 0.03), VAS (p = 0.003), and Tegner (p = 0.01) scores were greater in the AMIC group. No difference was found in the MOCART score (p = 0.08). The AMIC group evidenced lower rates of reoperation (p = 0.008) and failure (p = 0.003). CONCLUSION: At midterm follow-up, AMIC provides better results compared to MFx

A bargaining procedure leading to the serial rule in games with veto players

This paper studies an allocation procedure for coalitional games with veto players. The procedure is similar to the one presented by Arin and Feltkamp (J Math Econ 43:855-870, 2007), which is based on Dagan et al. (Games Econ Behav 18:55-72, 1997). A distinguished player makes a proposal that the remaining players must accept or reject, and conflict is solved bilaterally between the rejector and the proposer. We allow the proposer to make sequential proposals over several periods. If responders are myopic maximizers (i.e. consider each period in isolation), the only equilibrium outcome is the serial rule of Arin and Feltkamp (Eur J Oper Res 216:208-213, 2012) regardless of the order of moves. If all players are fully rational, the serial rule still arises as the unique subgame perfect equilibrium outcome if the order of moves is such that stronger players respond to the proposal after weaker ones

Structural Phase Transition at High Temperatures in Solid Molecular Hydrogen and Deuterium

We study the effect of temperature up to 1000K on the structure of dense molecular para-hydrogen and ortho-deuterium, using the path-integral Monte Carlo method. We find a structural phase transition from orientationally disordered hexagonal close packed (hcp) to an orthorhombic structure of Cmca symmetry before melting. The transition is basically induced by thermal fluctuations, but quantum fluctuations of protons (deuterons) are important in determining the transition temperature through effectively hardening the intermolecular interaction. We estimate the phase line between hcp and Cmca phases as well as the melting line of the Cmca solid.Comment: 8 pages, 7 figures; accepted in Phys. Rev.

Robotic milking technologies and renegotiating situated ethical relationships on UK dairy farms

Robotic or automatic milking systems (AMS) are novel technologies that take over the labor of dairy farming and reduce the need for human-animal interactions. Because robotic milking involves the replacement of 'conventional' twice-a-day milking managed by people with a system that supposedly allows cows the freedom to be milked automatically whenever they choose, some claim robotic milking has health and welfare benefits for cows, increases productivity, and has lifestyle advantages for dairy farmers. This paper examines how established ethical relations on dairy farms are unsettled by the intervention of a radically different technology such as AMS. The renegotiation of ethical relationships is thus an important dimension of how the actors involved are re-assembled around a new technology. The paper draws on in-depth research on UK dairy farms comparing those using conventional milking technologies with those using AMS. We explore the situated ethical relations that are negotiated in practice, focusing on the contingent and complex nature of human-animal-technology interactions. We show that ethical relations are situated and emergent, and that as the identities, roles, and subjectivities of humans and animals are unsettled through the intervention of a new technology, the ethical relations also shift. © 2013 Springer Science+Business Media Dordrecht

Remodelling of the angular collagen fiber distribution in cardiovascular tissues

Understanding collagen fiber remodelling is desired to optimize the mechanical conditioning protocols in tissue-engineering of load-bearing cardiovascular structures. Mathematical models offer strong possibilities to gain insight into the mechanisms and mechanical stimuli involved in these remodelling processes. In this study, a framework is proposed to investigate remodelling of angular collagen fiber distribution in cardiovascular tissues. A structurally based model for collagenous cardiovascular tissues is extended with remodelling laws for the collagen architecture, and the model is subsequently applied to the arterial wall and aortic valve. For the arterial wall, the model predicts the presence of two helically arranged families of collagen fibers. A branching, diverging hammock-type fiber architecture is predicted for the aortic valve. It is expected that the proposed model may be of great potential for the design of improved tissue engineering protocols and may give further insight into the pathophysiology of cardiovascular diseases