Blended Learning: Overview and Recommendations for Successful Implementation

Purpose – The purpose of this paper is to identify key themes within the blended learning literature and to develop a series of practical recommendations to facilitate the successful adaptation and implementation of a ‘‘blended approach to learning delivery’’. Design/methodology/approach – The literature was reviewed and informed a series of recommendations for organisations considering adopting or implementing blended approaches to teaching and training. Findings – Several key themes centering on the importance of evaluation, skills training, pedagogy, human factors, technology and implementation were identified. The emerging themes informed a series of practical recommendations to assist organisations considering blended learning approaches. Findings highlight the current limitations in the evidence base. Practical implications – The identified key themes and practical recommendations provide a useful assist to organisations considering adopting and implementing blended approaches to teaching and training. Originality/value – The paper highlights key areas for development in the blended learning literature and at the organisational level

LOS INTERESES DE SARKOZY Y LAS TRIBULACIONES DE LA POLÍTICA FRANCESA HACIA LIBIA

The French foreign policy process that accompanied the birth of the Fifth Republic and the collapse of the colonial system was inspired by the idea of greatness (grandeur de La France). National pride in the exercise of foreign policy, operated for many years as a counterweight to the decline of its international position as a power. However, from De Gaulle to Chirac, French policy was able to get some achievements based on a design that combined the national interest with the idea of grandeur. Although some scholars argue that “the foreign policy of no other Western state is driven by such narcissism” (Muravchick, 2007), other studies focus on the particularities of the French political system and the concept of monochromatic presidential government (Elgie & Griggs, 2000), a system of government in which the president decides the contents of the policy and is responsible for their successes and failures. For the Mediterranean region, the policy of the governments of the Fifth Republic acted on broadly similar principles until Nicolas Sarkozy came to power. Therefore, this paper focuses on the changes that occurred in the French position towards the Mediterranean region during the presidential term of Sarkozy and stresses the president’s unequivocal responsibility. Furthermore, the article emphasizes the direct engagement of France during the events in Libya in 2011 as the result of a personal interest rather than a foreign policy design

Attachment and prejudice: The mediating role of empathy

In two studies, we examined the novel hypothesis that empathy is a mechanism throughwhich the relationship between attachment patterns and prejudice can be explained.Study 1 examined primed attachment security (vs. neutral prime), empathy, and prejudicetowards immigrants. Study 2 examined primed attachment patterns (secure, avoidant,anxious), empathy subscales (perspective taking, empathic concern, personal distress),and prejudice towards Muslims. Across both studies, empathy mediated the relationshipbetween primed attachment security and low prejudice levels. The findings suggest thatenhancing felt security and empathic skills in individuals high in attachment–avoidance maylead to reduced prejudice

Allele-Specific HLA Loss and Immune Escape in Lung Cancer Evolution

Immune evasion is a hallmark of cancer. Losing the ability to present neoantigens through human leukocyte antigen (HLA) loss may facilitate immune evasion. However, the polymorphic nature of the locus has precluded accurate HLA copy-number analysis. Here, we present loss of heterozygosity in human leukocyte antigen (LOHHLA), a computational tool to determine HLA allele-specific copy number from sequencing data. Using LOHHLA, we find that HLA LOH occurs in 40% of non-small-cell lung cancers (NSCLCs) and is associated with a high subclonal neoantigen burden, APOBEC-mediated mutagenesis, upregulation of cytolytic activity, and PD-L1 positivity. The focal nature of HLA LOH alterations, their subclonal frequencies, enrichment in metastatic sites, and occurrence as parallel events suggests that HLA LOH is an immune escape mechanism that is subject to strong microenvironmental selection pressures later in tumor evolution. Characterizing HLA LOH with LOHHLA refines neoantigen prediction and may have implications for our understanding of resistance mechanisms and immunotherapeutic approaches targeting neoantigens. Video Abstract [Figure presented] Development of the bioinformatics tool LOHHLA allows precise measurement of allele-specific HLA copy number, improves the accuracy in neoantigen prediction, and uncovers insights into how immune escape contributes to tumor evolution in non-small-cell lung cancer

Fc-Optimized Anti-CD25 Depletes Tumor-Infiltrating Regulatory T Cells and Synergizes with PD-1 Blockade to Eradicate Established Tumors

CD25 is expressed at high levels on regulatory T (Treg) cells and was initially proposed as a target for cancer immunotherapy. However, anti-CD25 antibodies have displayed limited activity against established tumors. We demonstrated that CD25 expression is largely restricted to tumor-infiltrating Treg cells in mice and humans. While existing anti-CD25 antibodies were observed to deplete Treg cells in the periphery, upregulation of the inhibitory Fc gamma receptor (FcγR) IIb at the tumor site prevented intra-tumoral Treg cell depletion, which may underlie the lack of anti-tumor activity previously observed in pre-clinical models. Use of an anti-CD25 antibody with enhanced binding to activating FcγRs led to effective depletion of tumor-infiltrating Treg cells, increased effector to Treg cell ratios, and improved control of established tumors. Combination with anti-programmed cell death protein-1 antibodies promoted complete tumor rejection, demonstrating the relevance of CD25 as a therapeutic target and promising substrate for future combination approaches in immune-oncology

Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution.

The early detection of relapse following primary surgery for non-small-cell lung cancer and the characterization of emerging subclones, which seed metastatic sites, might offer new therapeutic approaches for limiting tumour recurrence. The ability to track the evolutionary dynamics of early-stage lung cancer non-invasively in circulating tumour DNA (ctDNA) has not yet been demonstrated. Here we use a tumour-specific phylogenetic approach to profile the ctDNA of the first 100 TRACERx (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy (Rx)) study participants, including one patient who was also recruited to the PEACE (Posthumous Evaluation of Advanced Cancer Environment) post-mortem study. We identify independent predictors of ctDNA release and analyse the tumour-volume detection limit. Through blinded profiling of postoperative plasma, we observe evidence of adjuvant chemotherapy resistance and identify patients who are very likely to experience recurrence of their lung cancer. Finally, we show that phylogenetic ctDNA profiling tracks the subclonal nature of lung cancer relapse and metastasis, providing a new approach for ctDNA-driven therapeutic studies

Fc Effector Function Contributes to the Activity of Human Anti-CTLA-4 Antibodies.

With the use of a mouse model expressing human Fc-gamma receptors (FcγRs), we demonstrated that antibodies with isotypes equivalent to ipilimumab and tremelimumab mediate intra-tumoral regulatory T (Treg) cell depletion in vivo, increasing the CD8+ to Treg cell ratio and promoting tumor rejection. Antibodies with improved FcγR binding profiles drove superior anti-tumor responses and survival. In patients with advanced melanoma, response to ipilimumab was associated with the CD16a-V158F high affinity polymorphism. Such activity only appeared relevant in the context of inflamed tumors, explaining the modest response rates observed in the clinical setting. Our data suggest that the activity of anti-CTLA-4 in inflamed tumors may be improved through enhancement of FcγR binding, whereas poorly infiltrated tumors will likely require combination approaches

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries