NFATc1/αA and Blimp-1 Support the Follicular and Effector Phenotype of Tregs

CD4+CXCR5+Foxp3+ T-follicular regulatory (TFR) cells control the germinal center responses. Like T-follicular helper cells, they express high levels of Nuclear Factor of Activated T-cells c1, predominantly its short isoform NFATc1/αA. Ablation of NFATc1 in Tregs prevents upregulation of CXCR5 and migration of TFR cells into B-cell follicles. By contrast, constitutive active NFATc1/αA defines the surface density of CXCR5, whose level determines how deep a TFR migrates into the GC and how effectively it controls antibody production. As one type of effector Treg, TFR cells express B lymphocyte-induced maturation protein-1 (Blimp-1). Blimp-1 can directly repress Cxcr5 and NFATc1/αA is necessary to overcome this Blimp-1-mediated repression. Interestingly, Blimp-1 even reinforces the recruitment of NFATc1 to Cxcr5 by protein-protein interaction and by those means cooperates with NFATc1 for Cxcr5 transactivation. On the contrary, Blimp-1 is necessary to counterbalance NFATc1/αA and preserve the Treg identity. This is because although NFATc1/αA strengthens the follicular development of Tregs, it bears the inherent risk of causing an ex-Treg phenotype.

Investigating the Use of Task Resumption Cues to Support Learning in Interruption-Prone Environments

The ubiquity of mobile devices in peoples’ everyday life makes them a feasible tool for language learning. Learning anytime and anywhere creates great flexibility but comes with the inherent risk of infrequent learning and learning in interruption-prone environments. No matter the length of the learning break, it can negatively affect knowledge consolidation and recall. This work presents the design and implementation of memory cues to support task resumption in mobile language learning applications and two evaluations to assess their impact on user experience. An initial laboratory experiment (N=15) revealed that while the presentation of the cues had no significant effect on objective performance measures (task completion time and error rate), the users still perceived the cues as helpful and would appreciate them in a mobile learning app. A follow-up study (N=16) investigated revised cue designs in a real-world field setting and found that users particularly appreciated our interactive test cue design. We discuss strengths and limitations of our concept and implications for the application of task resumption cues beyond the scope of mobile language learning.

Current and Novel Antiplatelet Therapies for the Treatment of Cardiovascular Diseases

Over the last decades, antiplatelet agents, mainly aspirin and P2Y12 receptor antagonists, have significantly reduced morbidity and mortality associated with arterial thrombosis. Their pharmacological characteristics, including pharmacokinetic/pharmacodynamics profiles, have been extensively studied, and a significant number of clinical trials assessing their efficacy and safety in various clinical settings have established antithrombotic efficacy. Notwithstanding, antiplatelet agents carry an inherent risk of bleeding. Given that bleeding is associated with adverse cardiovascular outcomes and mortality, there is an unmet clinical need to develop novel antiplatelet therapies that inhibit thrombosis while maintaining hemostasis. In this review, we present the currently available antiplatelet agents, with a particular focus on their targets, pharmacological characteristics, and patterns of use. We will further discuss the novel antiplatelet therapies in the pipeline, with the goal of improved clinical outcomes among patients with atherothrombotic diseases.

Deceptive advertising and its connection to unregulated gambling in the gaming industry

Streaming and on-demand entertainment content on new media platforms exposes viewers to gambling as influencers leverage audience’s trust within an insufficiently regulated industry. This article covers instances of influencers directing undisclosed endorsements for gamer gambling services to their audience, highlighting the presence of both inherent risk and of the need to regulate. On regulation, this article provides an evaluation of the regulatory framework already in place and whether consumers are sufficiently protected against deceptive advertising. It establishes a connection between undisclosed endorsements and unregulated gambling, in some cases involving minors. Lastly, it provides a thorough analysis on the effectiveness of the current regulatory framework as enforced by the FTC in the US and European influencer marketing legislation. This includes a discussion on the limitations of competent authorities to regulate in time juxtaposed by the strong interests of stakeholders within the gaming industry.

Understanding the Potential for Pharmacy Expertise in Palliative Care: The Value of Stakeholder Engagement in a Theoretically Driven Mapping Process for Research

Potentially avoidable medication-related harm is an inherent risk in palliative care; medication management accounts for approximately 20% of reported serious incidents in England and Wales. Despite their expertise benefiting patient care, the routine contribution of pharmacists in addressing medication management failures is overlooked. Internationally, specialist pharmacist support for palliative care services remains under-resourced. By understanding experienced practices (‘what happens in the real world’) in palliative care medication management, compared with intended processes (‘what happens on paper’), patient safety issues can be identified and addressed. This commentary demonstrates the value of stakeholder engagement and consultation work carried out to inform a scoping review and empirical study. Our overall goal is to improve medication safety in palliative care. Informal conversations were undertaken with carers and various specialist and non-specialist professionals, including pharmacists. Themes were mapped to five steps: decision-making, prescribing, monitoring and supply, use (administration), and stopping and disposal. A visual representation of stakeholders’ understanding of intended medicines processes was produced. This work has implications for our own and others’ research by highlighting where pharmacy expertise could have a significant additional impact. Evidence is needed to support best practice and implementation, particularly with regard to supporting carers in monitoring and accessing medication, and communication between health professionals across settings.

PENILAIAN KESEHATAN PERBANKAN SYARIAH

Perkembangan metodelogi penilaian tingkat kesehatan bank yang bersifat dinamis, tidak hanya dilakukan untuk bank konvensional saja, tetapi juga dilakukan untuk Bank Syariah baik untuk bank umum syariah maupun bank perkreditan rakyat syariah untuk mendorong pengaturan kembali sistem peniliaian tingkat kesehatan bank berdasarkan prinsip syariah. Dengan meningkatnya Eksposur resiko akan merubah profil resiko bank Sya yang pada gilirannya akan mempengaruhi tingkat kesehatan bank. Dalam penilaian tingkat kesehatan, Bank Syariah telah memasukkan risiko yang melekat pada aktivitas bank (inherent risk), yang merupakan bagian dari proses penilaian manajeman risiko.

Vibration-Induced Heating of Energetic Materials: A Review

The transport of energetic materials—whether by truck over rough terrain, or attached to the undercarriage of a high-performance jet aircraft—carries a certain level of inherent risk as the repeatedly applied stresses from vibration may lead to heating, mechanical degradation, and potentially even the triggering of an ignition event. Increasing knowledge of the underlying physics which control ignition is allowing us to better understand, and thus reduce, the risk of a catastrophic event occurring. The Apollo and Space Shuttle programmes provided motivation for research into the topic in the 1960s and 1970s, and some recent studies have focussed on the grain-scale physics of ignition. However, much of the useful insight has arisen from work with other primary applications in mind. Therefore, this review aims to bring together literature from several fields, with the intention of better understanding vibration-induced heating (VIH) phenomena in energetic materials. Sensitivity, VIH in viscoelastic polymers and inert composites, and a technique known as vibrothermography which uses VIH to detect cracks, are all considered where relevant read-across can be found. Often being viscoelastic materials and composites with complex rheology, energetic materials subjected to vibrational loading tend to warm up, with potential for even greater temperature rises due to anisotropy-driven localised heating mechanisms. Binders soften as temperature rises, and the chance of damage increases, which may lead to runaway heating and thermal failure (if mechanical failure does not occur first).

Risk Assessment Algorithm for Power Transformer Fleets Based on Condition and Strategic Importance

In every electric power system, power transformers (PT) play a critical role. Under ideal circumstances, PT should receive the utmost care to maintain the highest operative condition during their lifetime. Through the years, different approaches have been developed to assess the condition and the inherent risk during the operation of PT. However, most proposed methodologies tend to analyze PT as individuals and not as a fleet. A fleet assessment helps the asset manager make sound decisions regarding the maintenance scheduling for groups of PT with similar conditions. This paper proposes a new methodology to assess the risk of PT fleets, considering the technical condition and the strategic importance of the units. First, the state of the units was evaluated using a health index (HI) with a fuzzy logic algorithm. Then, the strategic importance of each unit was assessed using a weighting technique to obtain the importance index (II). Finally, the analyzed units with similar HI and II were arranged into a set of clusters using the k-means clustering technique. A fleet of 19 PTs was used to validate the proposed method. The obtained results are also provided to demonstrate the viability and feasibility of the assessment model.

EP.TU.560Improving surgical handover by implementing a dynamic handover sheet

Aim Safe and effective handover is paramount to ensuring good patient care and patient safety. The aim of this study was to identify key issues with the current handover sheets and implement a new comprehensive sheet aimed to improve quality of handover and reduce safety issues within a busy DGH general surgery department. Methods A prospective dynamic study was performed. Retrospective data was obtained by sending out questionnaires to all junior and senior staff. The questionnaire aimed to assess key issues with the original handover sheets and collect qualitative data of perceived safety and efficiency. A dynamic handover sheet was developed using Microsoft Excel and Microsoft Visual Basic. After 2 months of using the new handover sheet, repeat questionnaires were sent out to assess its impact. Results There were 26 responses to the pre-intervention and 14 to the post-intervention questionnaire. 14/26 (54%) reported safety issues, mainly patients being missed at weekend ward rounds or missing handovers from elective teams. Post introduction of the comprehensive sheet 6/14 (43%) reported safety issues, mostly related to user error. Subjective list accuracy improved from 59.0% to 65.3% and accuracy for weekend wardrounds improved from 58.4% to 61.3%. Subjective efficiency of the list improved from 52.5% to 71.5%. Conclusion The new, dynamic handover sheet has led to an overall improvement in safety and efficiency of handover. An easy to understand instruction sheet has been designed to further improve usability and to ensure a lasting effect to mitigate against the inherent risk of junior doctor change-over.