Two-Stage Priming of Allogeneic Natural Killer Cells for the Treatment of Patients with Acute Myeloid Leukemia: A Phase I Trial

Human Natural Killer (NK) cells require at least two signals to trigger tumor cell lysis. Absence of ligands providing either signal 1 or 2 provides NK resistance. We manufactured a lysate of a tumour cell line which provides signal 1 to resting NK cells without signal 2. The tumor-primed NK cells (TpNK) lyse NK resistant Acute Myeloid Leukemia (AML) blasts expressing signal 2 ligands. We conducted a clinical trial to determine the toxicity of TpNK cell infusions from haploidentical donors. 15 patients with high risk AML were screened, 13 enrolled and 7 patients treated. The remaining 6 either failed to respond to re-induction chemotherapy or the donor refused to undergo peripheral blood apheresis. The conditioning consisted of fludarabine and total body irradiation. This was the first UK trial of a cell therapy regulated as a medicine. The complexity of Good Clinical Practice compliance was underestimated and led to failures requiring retrospective independent data review. The lessons learned are an important aspect of this report. There was no evidence of infusional toxicity. Profound myelosuppression was seen in the majority (median neutrophil recovery day 55). At six months follow-up, three patients treated in Complete Remission (CR) remained in remission, one patient infused in Partial Remission had achieved CR1, two had relapsed and one had died. One year post-treatment one patient remained in CR. Four patients remained in CR after treatment for longer than their most recent previous CR. During the 2 year follow-up six of seven patients died; median overall survival was 400 days post infusion (range 141–910). This is the first clinical trial of an NK therapy in the absence of IL-2 or other cytokine support. The HLA-mismatched NK cells survived and expanded in vivo without on-going host immunosuppression and appeared to exert an anti-leukemia effect in 4/7 patients treated

Collective victimhood in populist media about Brexit: rage against the machine?

This paper outlines an ongoing qualitative study in social psychology, with a pilot study completed and the main study currently at the data analysis stage. We examine how collective and competitive victimhood are invoked in populist rhetoric and media coverage of the United Kingdom’s departure from the European Union (Brexit). Brexit has been portrayed by its proponents as a project on behalf of ordinary British people against an out-of-touch liberal elite and a malevolent European Union (EU), with the opposing campaign to remain in the EU commonly characterised as an alarmist “project fear” (see Bartholomew, 2017; Durrheim et al., 2018; Forsyth, 2016; Malik, 2018). This populist idea of ordinary people as victims of manipulative and mendacious elites seems to relate to social-psychological work on collective and competitive victimhood (Bar-Tal et al., 2009; Noor et al., 2008a, 2008b, 2012; Vollhardt et al., 2014). According to this account, victimhood can be used as political capital to justify grievances and intergroup conflict. Research on this topic has mostly used quantitative methods, but first attempts have been made to use qualitative methods to show rhetorical functions of collective and competitive victimhood (McNeill et al., 2017). Building on these theoretical and methodological foundations, we use thematic analysis and discourse analysis to show how victimhood is mobilised in British media to garner support for Brexit, and how this connects with concepts such as collective relative deprivation (e.g. Abrams & Grant, 2012; Runciman, 1966) and relative gratification (Dambrun et al., 2006; Guimond & Dambrun, 2002; Jetten et al., 2015). In doing so, we contribute to a social-psychological perspective on Brexit, develop further the concepts of collective and competitive victimhood, and connect the micro-level of language used in the media sphere to the macro-level of populist movements in democratic societies

Analysis of local seismic response in the historical city centre of Nafplio (Greece)

Local seismic response analysis represents a fundamental tool for assessing the seismic risk of urban areas and Cultural Heritage (CH) sites, nevertheless several open questions remain when complex geological contexts are considered. This study has been carried out in the framework of the research project STABLE (H2020 RISE-Marie Curie Action) which has the aim of evaluating the seismic action on CH sites in the Mediterranean basin. One of them being the city of Nafplio (Greece), a site characterised by a peculiar geological setting and a medium-high regional seismic hazard. Geological and geophysical data have been collected to reconstruct both the subsoil model and the seismotectonic conditions. Several seismic ambient noise measurements were carried out to establish the site resonance frequency and to validate engineering-geological cross-sections for numerical modelling of the seismic wave propagation. Combined engineering-geological, geophysical and numerical modelling allowed evaluating the local seismic response of the urban area of Nafplio, providing a zonation map with homogeneous seismic response zones for which elastic response spectra will be obtained

The RISKMED project : philosophy, methods and products

This paper presents RISKMED, a project targeted to create an Early Warning System (EWS) in case of severe or extreme weather events in the central and eastern Mediterranean and specifically in southern Italy, northwestern Greece, Malta and Cyprus. As severe or extreme weather events are considered, cases when the values of some meteorological parameters (temperature, wind, precipitation) exceed certain thresholds, and/or a severe weather phenomenon (thunderstorm, snowfall) occurs. For an accurate weather forecast, selected meteorological models have been operated daily, based on a nesting strategy using two or three domains, providing detailed forecasts over the above mentioned areas. The forecast results are further exploited for the evaluation and prediction of human discomfort and fire weather indices. Finally, sea wave models have also been operating daily over the central and eastern Mediterranean Sea. In case a severe or extreme weather event is forecasted within the next 48 or 72 h for selected target areas (sub-regions defined by their morphological and population characteristics), the local authorities and the public are informed via a user-friendly graphic system, the so-called RISK MAP. On the web page of the Project (http://www.riskmed.net), additional information is provided about the real-time values of some meteorological parameters, the latest satellite picture and the time and space distribution of lightning during the last 24 h. The RISKMED project was financed by the EU and the Ministries of National Economy of Greece, Italy, Malta and Cyprus, in the frame of INTERREG IIIB/ARCHIMED programme.peer-reviewe

Abscess formation of a spherical-shape duplication in the splenic flexure of the colon: case report and review of the literature

Gastrointestinal tract duplications are rare congenital malformations that may occur anywhere in the alimentary tract from the mouth to the anus, and vary greatly in presentation, size, location, and especially in symptoms. We present a case of an infected spherical colonic duplication, in a 20-day-old baby, located at the splenic flexure of the colon. The prominent symptom was acute abdomen, accompanied by bilious vomiting, intestinal obstruction, and high fever. We present this case, due to atypical clinical presentation and the inability of the imaging modality to establish the diagnosis preoperatively

Bottom up ethics - neuroenhancement in education and employment

Neuroenhancement involves the use of neurotechnologies to improve cognitive, affective or behavioural functioning, where these are not judged to be clinically impaired. Questions about enhancement have become one of the key topics of neuroethics over the past decade. The current study draws on in-depth public engagement activities in ten European countries giving a bottom-up perspective on the ethics and desirability of enhancement. This informed the design of an online contrastive vignette experiment that was administered to representative samples of 1000 respondents in the ten countries and the United States. The experiment investigated how the gender of the protagonist, his or her level of performance, the efficacy of the enhancer and the mode of enhancement affected support for neuroenhancement in both educational and employment contexts. Of these, higher efficacy and lower performance were found to increase willingness to support enhancement. A series of commonly articulated claims about the individual and societal dimensions of neuroenhancement were derived from the public engagement activities. Underlying these claims, multivariate analysis identified two social values. The Societal/Protective highlights counter normative consequences and opposes the use enhancers. The Individual/Proactionary highlights opportunities and supports use. For most respondents these values are not mutually exclusive. This suggests that for many neuroenhancement is viewed simultaneously as a source of both promise and concern

What is damaging the kidney in lupus nephritis?

Despite marked improvements in the survival of patients with severe lupus nephritis over the past 50 years, the rate of complete clinical remission after immune suppression therapy i

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700