Exploring Critical Perspectives of Toxic and Bad Leadership Through Film

© 2015, © The Author(s) 2015. The Problem This article considers concepts of toxic and bad leadership from a critical, post-structuralist perspective and illustrates how this can be conveyed to management students through the use of film analysis. In response to the paucity of critical approaches within toxic and bad leadership studies, we suggest that film is a useful way of developing in-depth discussion in student and management groups to uncover underlying subtleties and complexity in leadership theory and practice. The Solution We connect to film clips from Batman: The Dark Knight, and explain how this film is used with students and managers to illustrate the ambiguous nature of “good” and “bad” leadership and explore the fluid, shifting, and relational nature of these two concepts. We conclude that students and managers can recognize this more readily through viewing, discussing, and analyzing film clips such as the ones discussed herein. The Stakeholders University lecturers and students, executive educators and managers, general human resource development (HRD) professional

The Antarctic Peninsula Under a 1.5°C Global Warming Scenario

Warming of the Antarctic Peninsula in the latter half of the twentieth century was greater than any other terrestrial environment in the Southern Hemisphere, and clear cryospheric and biological consequences have been observed. Under a global 1.5°C scenario, warming in the Antarctic Peninsula is likely to increase the number of days above 0°C, with up to 130 of such days each year in the northern Peninsula. Ocean turbulence will increase, making the circumpolar deep water (CDW) both warmer and shallower, delivering heat to the sea surface and to coastal margins. Thinning and recession of marine margins of glaciers and ice caps is expected to accelerate to terrestrial limits, increasing iceberg production, after which glacier retreat may slow on land. Ice shelves will experience continued increase in meltwater production and consequent structural change, but not imminent regional collapses. Marine biota can respond in multiple ways to climatic changes, with effects complicated by past resource extraction activities. Southward distribution shifts have been observed in multiple taxa during the last century and these are likely to continue. Exposed (ice free) terrestrial areas will expand, providing new habitats for native and non-native organisms, but with a potential loss of genetic diversity. While native terrestrial biota are likely to benefit from modest warming, the greatest threat to native biodiversity is from non-native terrestrial species

Intensification of coffee systems can increase the effectiveness of REDD mechanisms

In agricultural production systems with shade trees, such as coffee, the increase in greenhouse gas (GHG) emissions from production intensification can be compensated for, or even outweighed, by the increase in carbon sequestration into above-ground and below-ground tree biomass. We use data from a long-term coffee agroforestry experiment in Costa Rica to evaluate the trade-offs between intensification, profitability and net greenhouse gas emissions through two scenarios. First, by assessing the GHG emissions associated with conversion from shaded to more profitable full-sun (un-shaded) systems, we calculate the break-even carbon price which would need to be paid to offset the opportunity cost of not converting. The price per tCO2e of emissions reduction required to compensate for the coffee production revenue foregone varies widely from 9.3 to 196.3 US$ amongst different shaded systems. Second, as an alternative to intensification, production area can be extended onto currently forested land. We estimate this land-use change required to compensate for the shortfall in profitability from retaining lower intensity coffee production systems. For four of the five shade types tested, this land-use change causes additional GHG emissions >5 tCO2e ha−1 yr−1 resulting in net emissions >8 tCO2e ha−1 yr−1 for the whole system. We conclude that instead, by intensifying production, mechanisms similar to REDD that are based on reducing emissions through avoided land-use change (REAL) could play a major role in increasing the climate change mitigation success of agroforestry systems at the same time as aiding REDD through reducing pressure for further forest conversion to agriculture

Greenhouse gas emissions in coffee grown with differing input levels under conventional and organic management

Coffee plays a key role in sustaining millions of livelihoods around the world. Understanding GHG emissions from coffee supply chains is important in evaluating options for climate change mitigation within the sector. We use data from two long-term coffee agroforestry experiments in Costa Rica and Nicaragua to calculate carbon footprints (CF) for coffee and identify emission hotspots within different management systems, levels of inputs and shade types. Management system and input level were the main cause of variation in CFs. Carbon footprints for 1 kg of fresh coffee cherries were between 0.26 and 0.67 kgCO2e for conventional and 0.12 and 0.52 kgCO2e for organic management systems. The main contributor to GHG emissions for all management systems was the inputs of organic and inorganic nitrogen. Nitrous oxide emissions from pruning inputs contributed between 7% and 42 % of CFs. However, these estimates were strongly influenced by the choice of emission factors

Environmental justice and transformations to sustainability

Global carbon emissions continue to rise,1 rates of global biodiversity loss continue to increase,2 and social and economic inequalities continue to widen.3 Significant global social movements such as Fridays for Future are declaring this situation an “emergency,” regarding it as a crime against humanity in which political and business leaders stand accused of ignoring the plight of current and future vulnerable people. This association between environmental crises and social injustice is now widely accepted. Many feel that time is running out for incremental approaches to prove effective and that there is an inescapable need for a radical, transformative change that combines sustainability and justice

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

Cerebral microbleeds and intracranial haemorrhage risk in patients anticoagulated for atrial fibrillation after acute ischaemic stroke or transient ischaemic attack (CROMIS-2):a multicentre observational cohort study

Background: Cerebral microbleeds are a potential neuroimaging biomarker of cerebral small vessel diseases that are prone to intracranial bleeding. We aimed to determine whether presence of cerebral microbleeds can identify patients at high risk of symptomatic intracranial haemorrhage when anticoagulated for atrial fibrillation after recent ischaemic stroke or transient ischaemic attack. Methods: Our observational, multicentre, prospective inception cohort study recruited adults aged 18 years or older from 79 hospitals in the UK and one in the Netherlands with atrial fibrillation and recent acute ischaemic stroke or transient ischaemic attack, treated with a vitamin K antagonist or direct oral anticoagulant, and followed up for 24 months using general practitioner and patient postal questionnaires, telephone interviews, hospital visits, and National Health Service digital data on hospital admissions or death. We excluded patients if they could not undergo MRI, had a definite contraindication to anticoagulation, or had previously received therapeutic anticoagulation. The primary outcome was symptomatic intracranial haemorrhage occurring at any time before the final follow-up at 24 months. The log-rank test was used to compare rates of intracranial haemorrhage between those with and without cerebral microbleeds. We developed two prediction models using Cox regression: first, including all predictors associated with intracranial haemorrhage at the 20% level in univariable analysis; and second, including cerebral microbleed presence and HAS-BLED score. We then compared these with the HAS-BLED score alone. This study is registered with ClinicalTrials.gov, number NCT02513316. Findings: Between Aug 4, 2011, and July 31, 2015, we recruited 1490 participants of whom follow-up data were available for 1447 (97%), over a mean period of 850 days (SD 373; 3366 patient-years). The symptomatic intracranial haemorrhage rate in patients with cerebral microbleeds was 9·8 per 1000 patient-years (95% CI 4·0–20·3) compared with 2·6 per 1000 patient-years (95% CI 1·1–5·4) in those without cerebral microbleeds (adjusted hazard ratio 3·67, 95% CI 1·27–10·60). Compared with the HAS-BLED score alone (C-index 0·41, 95% CI 0·29–0·53), models including cerebral microbleeds and HAS-BLED (0·66, 0·53–0·80) and cerebral microbleeds, diabetes, anticoagulant type, and HAS-BLED (0·74, 0·60–0·88) predicted symptomatic intracranial haemorrhage significantly better (difference in C-index 0·25, 95% CI 0·07–0·43, p=0·0065; and 0·33, 0·14–0·51, p=0·00059, respectively). Interpretation: In patients with atrial fibrillation anticoagulated after recent ischaemic stroke or transient ischaemic attack, cerebral microbleed presence is independently associated with symptomatic intracranial haemorrhage risk and could be used to inform anticoagulation decisions. Large-scale collaborative observational cohort analyses are needed to refine and validate intracranial haemorrhage risk scores incorporating cerebral microbleeds to identify patients at risk of net harm from oral anticoagulation. Funding: The Stroke Association and the British Heart Foundation

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