Control of stochastic and induced switching in biophysical networks

Noise caused by fluctuations at the molecular level is a fundamental part of intracellular processes. While the response of biological systems to noise has been studied extensively, there has been limited understanding of how to exploit it to induce a desired cell state. Here we present a scalable, quantitative method based on the Freidlin-Wentzell action to predict and control noise-induced switching between different states in genetic networks that, conveniently, can also control transitions between stable states in the absence of noise. We apply this methodology to models of cell differentiation and show how predicted manipulations of tunable factors can induce lineage changes, and further utilize it to identify new candidate strategies for cancer therapy in a cell death pathway model. This framework offers a systems approach to identifying the key factors for rationally manipulating biophysical dynamics, and should also find use in controlling other classes of noisy complex networks.Comment: A ready-to-use code package implementing the method described here is available from the authors upon reques

Getting Psyched About Memes in the Psychology Classroom

Introduction: Internet memes are a ubiquitous part of internet culture and a common communication tool among students. Because they are a good medium for expressing ideas and concepts in a concise and fun manner, memes are a potentially valuable tool for teaching and engaging students. Statement of the Problem: Instructors may not know how to use memes in classroom assignments or activities to support learning objectives. Literature Review: Students finding or creating their own class-related content is an empirically-supported way to enhance learning. Instructors can enhance learning by using multimedia approaches (pictures/videos in addition to words), which is a good fit for the use of memes. We include examples of ways that memes have already been used in psychology classrooms. Teaching Implications: Incorporating meme assignments or activities in the classroom could be beneficial. Conclusion: We describe how students can explain or generate memes that illustrate concepts related to course material. Instructions and supporting information and resources, as well as calls for research into the effectiveness of the use of memes in the classroom, are included

Anti-TNF therapy is associated with an increased risk of serious infections in patients with rheumatoid arthritis especially in the first 6 months of treatment: updated results from the British Society for Rheumatology Biologics Register with special emphasis on risks in the elderly

Objectives. To evaluate the risk of serious infections (SIs) in patients with RA treated with anti-TNF therapy with emphasis on the risk across different ages

Concurrent Oral 1 - Rheumatoid Arthritis: Treatment [OP4-OP9]: OP4. Inhibition of Radiographic Progression and Improvements in Physical Function at 2 Years, with Increasing Clinical Efficacy Over Time, in Rheumatoid Arthritis (Ra) Patients Treated with Tocilizumab (Tcz): The Lithe Study

Background: Patients with moderate to severe RA who remained on methotrexate (MTX) despite inadequate response were treated with TCZ in a double-blind, randomized, controlled phase 3 trial. Results of a 2-year planned analysis from this study are presented. Methods: Patients were randomized to treatment with TCZ 4 mg/kg + MTX (TCZ4), TCZ 8 mg/kg + MTX (TCZ8) or placebo + MTX (CON) every 4 weeks. If patients failed to respond ( 60% of patients and the DAS28 remission (DAS28 < 2.6) rate was 48% at week 52 and continued to increase to week 104. By week 52, patients treated with TCZ8 had clinically significant improvements in SJC that were maintained through week 104. Rates per 100 PY for adverse events (AEs) were higher in TCZ8 and TCZ4 (263.6, 275.4) vs CON patients (251.4) while rates for serious AEs were comparable (11.4, 12.1, 10.9, respectively). Rates per 100 PY of AEs leading to withdrawal (7.4, 32.5, 4.8) and treatment modification (8.4, 30.7, 20.4) were higher in TCZ8 and TCZ4 vs CON patients, respectively and death rates were comparable (0.6, 0.2, 0.4). Conclusions: Treatment with TCZ + MTX inhibits radiographic progression over 2 years and improves physical function as shown by DAS28 remission, LDAS and low SJC, with a manageable safety profile. Disclosure statement: E.A., F. Hoffmann-La Roche - Employee. P.A., F. Hoffmann-La Roche - Employee. R.B.-V., F. Hoffmann-La Roche - Honoraria. R.F., Genentech - Research Funding, Honoraria. J.K., F. Hoffmann-La Roche - Research funding, Honorari

Mental health training programmes for non-mental health trained professionals coming into contact with people with mental ill health: a systematic review of effectiveness

Background The police and others in occupations where they come into close contact with people experiencing/with mental ill health, often have to manage difficult and complex situations. Training is needed to equip them to recognise and assist when someone has a mental health issue or learning/intellectual disability. We undertook a systematic review of the effectiveness of training programmes aimed at increasing knowledge, changing behaviour and/or attitudes of the trainees with regard to mental ill health, mental vulnerability, and learning disabilities. Methods Databases searched from 1995 onwards included: ASSIA, Cochrane Central Register of Controlled Clinical Trials (CENTRAL), Criminal Justice Abstracts, Embase, ERIC, MEDLINE, PsycINFO, Social Science Citation Index. Courses, training, or learning packages aimed at helping police officers and others who interact with the public in a similar way to deal with people with mental health problems were included. Primary outcomes were change in practice and change in outcomes for the groups of people the trainees come into contact with. Systematic reviews, randomised controlled trials (RCTs) and non- randomised controlled trials (non-RCTs) were included and quality assessed. In addition non-comparative evaluations of training for police in England were included. Results From 8578 search results, 19 studies met the inclusion criteria: one systematic review, 12 RCTs, three prospective non-RCTs, and three non-comparative studies. The training interventions identified included broad mental health awareness training and packages addressing a variety of specific mental health issues or conditions. Trainees included police officers, teachers and other public sector workers. Some short term positive changes in behaviour were identified for trainees, but for the people the trainees came into contact with there was little or no evidence of benefit. Conclusions A variety of training programmes exist for non-mental health professionals who come into contact with people who have mental health issues. There may be some short term change in behaviour for the trainees, but longer term follow up is needed. Research evaluating training for UK police officers is needed in which a number of methodological issues need to be addressed

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy