An analysis of task assignment and cycle times when robots are added to human-operated assembly lines, using mathematical programming models

Abstract Adding robots to a human-operated assembly line influences both the short- and long-term operation of the line. However, the effects of robots on assembly line capacity and on cycle time can only be studied if appropriate task assignment models are available. This paper shows how traditional assembly line balancing models can be changed in order to determine the optimal number of workstations and cycle time when robots with different technological capabilities are able to perform a predetermined set of tasks. The mathematical programming models for the following three cases are presented and analysed: i) only workers are assigned to the workstations; ii) either a worker or a robot is assigned to a workstation; iii) a robot and a worker are also assigned to specific workstations. The data of an assembly line producing power inverters is used to illustrate the proposed calculations. Both the assignment of tasks and the changes of cycle time are analysed within the AIMMS modelling environment. The computational characteristics of the proposed mathematical programming models are also examined and tested using benchmark problems. The models presented in this paper can assist operations management in making decisions relating to assembly line configuration

Effects of the mu-opioid receptor antagonist GSK1521498 on hedonic and consummatory eating behaviour: a proof of mechanism study in binge-eating obese subjects.

The opioid system is implicated in the hedonic and motivational processing of food, and in binge eating, a behaviour strongly linked to obesity. The aim of this study was to evaluate the effects of 4 weeks of treatment with the mu-opioid receptor antagonist GSK1521498 on eating behaviour in binge-eating obese subjects. Adults with body mass index ⩾30 kg m−2 and binge eating scale scores ⩾19 received 1-week single-blind placebo run-in, and were then randomized to 28 days with either 2 mg day−1 GSK1521498, 5 mg day−1 GSK1521498 or placebo (N=21 per arm) in a double-blind parallel group design. The outcome measures were body weight, fat mass, hedonic and consummatory eating behaviour during inpatient food challenges, safety and pharmacokinetics. The primary analysis was the comparison of change scores in the higher-dose treatment group versus placebo using analysis of covariance at each relevant time point. GSK1521498 (2 mg and 5 mg) was not different from placebo in its effects on weight, fat mass and binge eating scores. However, compared with placebo, GSK1521498 5 mg day−1 caused a significant reduction in hedonic responses to sweetened dairy products and reduced calorific intake, particularly of high-fat foods during ad libitum buffet meals, with some of these effects correlating with systemic exposure of GSK1521498. There were no significant effects of GSK1521498 2 mg day−1 on eating behaviour, indicating dose dependency of pharmacodynamics. GSK1521498 was generally well tolerated and no previously unidentified safety signals were detected. The potential for these findings to translate into clinically significant effects in the context of binge eating and weight regain prevention requires further investigation

New Pharmacological Agents to Aid Smoking Cessation and Tobacco Harm Reduction: What has been Investigated and What is in the Pipeline?

A wide range of support is available to help smokers to quit and aid attempts at harm reduction, including three first-line smoking cessation medications: nicotine replacement therapy, varenicline and bupropion. Despite the efficacy of these, there is a continual need to diversify the range of medications so that the needs of tobacco users are met. This paper compares the first-line smoking cessation medications to: 1) two variants of these existing products: new galenic formulations of varenicline and novel nicotine delivery devices; and 2) twenty-four alternative products: cytisine (novel outside of central and eastern Europe), nortriptyline, other tricyclic antidepressants, electronic cigarettes, clonidine (an anxiolytic), other anxiolytics (e.g. buspirone), selective 5-hydroxytryptamine (5-HT) reuptake inhibitors, supplements (e.g. St John’s wort), silver acetate, nicobrevin, modafinil, venlafaxine, monoamine oxidase inhibitors (MAOI), opioid antagonist, nicotinic acetylcholine receptors (nAChR) antagonists, glucose tablets, selective cannabinoid type 1 receptor antagonists, nicotine vaccines, drugs that affect gamma-aminobutyric acid (GABA) transmission, drugs that affect N-methyl-D-aspartate receptors (NMDA), dopamine agonists (e.g. levodopa), pioglitazone (Actos; OMS405), noradrenaline reuptake inhibitors, and the weight management drug lorcaserin. Six criteria are used: relative efficacy, relative safety, relative cost, relative use (overall impact of effective medication use), relative scope (ability to serve new groups of patients), and relative ease of use (ESCUSE). Many of these products are in the early stages of clinical trials, however, cytisine looks most promising in having established efficacy and safety and being of low cost. Electronic cigarettes have become very popular, appear to be efficacious and are safer than smoking, but issues of continued dependence and possible harms need to be considered

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Kardiale Antigene und T-Zell Spezifität nach experimentellem Myokardinfarkt in Mäusen

Cardiovascular diseases (CVD), subsuming atherosclerosis of the coronary arteries and subsequent myocardial infarction, are the leading cause of death in the European Union (over 4 million deaths annually), with devastating individual and economic consequences. Recent studies revealed that T cells play a crucial role in post-MI inflammation, healing and remodelling processes. Nevertheless, the specificity profile of adaptive immune responses in the infarcted myocardium has not yet been differentiated. The experiments portrayed in this thesis sought to assess whether post-MI CD4+ T cell responses in mice are triggered by heart specific antigens, and eventually identify relevant epitopes. We were able to create a murine antigen atlas including a list of 206 epitopes for I-Ab and 193 epitopes for I-Ad presented on MHC-II in the context of MI. We sought to consecutively test this panel by in vitro T cell proliferation and antigen recall assays ex vivo. The elispot assay was used as a readout for antigen-specific stimulation by measurement of IL-2 and IFN-γ production, currently the most sensitive approach available to detect even small counts of antigen producing cells. Splenocytes as well as lymphocytes from mediastinal lymph nodes were purified from animals 7 days or 56 days after EMI conducted by ligation of the left anterior descending artery. We were able to provide evidence that post-MI T cell responses in Balb/c mice are triggered by heart-specific antigens and that MYHCA, especially MYHCA614-628, is relevant for that response. Moreover, a significant specific T cell response after MI in C57BL/6J mice was observed for α actin, cardiac muscle 1 [ACTC1], myosin-binding protein C3 [MYBPC3] and myosin heavy chain α [MYHCA] derived heart specific antigens. Generally, the epitopes of interest for Balb/c as well as C57BL/6J could be further investigated and may eventually be modulated in the future.Herz-Kreislauf-Erkrankungen (CVD) sowie der häufig folgende Myokardinfarkt sind die häufigsten Todesursachen in der Europäischen Union (über 4 Millionen Todesfälle pro Jahr) mit verheerenden individuellen und wirtschaftlichen Folgen. Aktuelle Studien haben gezeigt, dass T-Zellen eine entscheidende Rolle bei Entzündungs-, Heilungs- und Umbauprozessen nach einem Myokardinfarkt spielen. Das Spezifitätsprofil adaptiver Immunantworten im infarzierten Myokard konnte bisher jedoch noch nicht differenziert werden. Die in dieser Arbeit dargestellten Experimente gingen der Frage nach, ob CD4+ T-Zellantworten nach einem Myokardinfarkt in Mäusen durch herzspezifische Antigene ausgelöst werden und ob hieraus relevante Epitope identifiziert werden können. Uns gelang es, einen Maus-Antigen-Atlas zu erstellen, der eine Zusammenstellung von 206 Epitopen für I-Ab und 193 Epitope für I-Ad enthält, welche auf MHC-II im Rahmen des Myokardinfarkts präsentiert werden. Dieses Panel wurde nacheinander durch In-vitro-T-Zell-Proliferations- und Antigen-Recall-Assays ex vivo getestet. Der Elispot-Assay wurde als sensitivster verfügbare Ansatz zur Quantifizierung der antigen-spezifischen Stimulation durch Messung der IL-2- und IFN-γ-Produktion verwendet. Splenozyten sowie Lymphozyten aus mediastinalen Lymphknoten der Mäuse wurden 7 Tage bzw. 56 Tage nach einem experimentellen Myokardinfarkt, welcher durch Ligation der RIVA Arterie durchgeführt wurde, aufgereinigt. Wir konnten nachweisen, dass Post-MI-T-Zellantworten in Balb/c Mäusen durch herzspezifische Antigene ausgelöst werden, und dass MYHCA, insbesondere MYHCA614-628, für diese Antwort relevant ist. Darüber hinaus konnte eine signifikante spezifische T-Zell-Antwort nach Myokardinfarkt in C57BL/6J Mäusen auf aus Alpha-Actin des Herzmuskels 1 [ACTC1], Myosin-bindendes Protein C vom Herztyp [MYBPC3] und der schweren Kette des Myosins α [MYHCA] generierten herzspezifischen Antigenen gezeigt werden

Defining a synovial fluid white blood cell count threshold to predict periprosthetic infection after shoulder arthroplasty

Background: The diagnosis of periprosthetic shoulder infection (PSI) requires a thorough diagnostic workup. Synovial fluid aspiration has been proven to be a reliable tool in the diagnosis of joint infections of the lower extremity, but shoulder specific data is limited. This study defines a threshold for synovial fluid white blood cell count (WBC) and assesses the reliability of microbiological cultures. Methods: Retrospective study of preoperative and intraoperative fluid aspiration of 31 patients who underwent a revision of a shoulder arthroplasty (15 with PSI defined by IDSA criteria, 16 without infection). The threshold for WBC was calculated by ROC/AUC analysis. Results: WBC was significantly higher in patients with PSI than in other patients. A threshold of 2800 leucocytes/mm$^3$ showed a sensitivity of 87% and a specificity of 88% (AUROC 0.92). Microbiological cultures showed a sensitivity of 76% and a specificity of 100%. Conclusions: A threshold of 2800 leucocytes/mm$^3$ in synovial fluid can be recommended to predict PSI. Microbiological culture has an excellent specificity and allows for targeted antibiotic therapy. Joint aspiration presents an important pillar to diagnose PSI

Myocardial infarction triggers cardioprotective antigen-specific T helper cell responses

T cell autoreactivity is a hallmark of autoimmune diseases but can also benefit self-maintenance and foster tissue repair. Here, we investigated whether heart-specific T cells exert salutary or detrimental effects in the context of myocardial infarction (MI), the leading cause of death worldwide. After screening more than 150 class II–restricted epitopes, we found that myosin heavy chain α (MYHCA) was a dominant cardiac antigen triggering post-MI CD4+ T cell activation in Balb/c mice. Transferred MYHCA 614–629-specific CD4+ T cells (TCR-M cells) selectively accumulated in the myocardium and mediastinal lymph nodes (med-LNs) of infarcted mice, acquired a Treg phenotype with a distinct prohealing gene expression profile, and mediated cardioprotection. Myocardial Tregs were also detected in autopsy samples from patients who had had a MI. Noninvasive PET/CT imaging using a CXCR4 radioligand revealed enlarged med-LNs with increased cellularity in patients with MI. Notably, the med-LN alterations observed in MI patients correlated with the infarct size and cardiac function. Taken together, the results obtained in our study provide evidence that MI context induces prohealing T cell autoimmunity in mice and confirm the existence of an analogous heart/med-LN/T cell axis in patients with MI