Developing a corpus of strategic conversation in The Settlers of Catan

International audienceWe describe a dialogue model and an implemented annotation scheme for a pilot corpus of annotated online chats concerning bargaining negotiations in the game The Settlers of Catan. We will use this model and data to analyze how conversations proceed in the absence of strong forms of cooperativity, where agents have diverging motives. Here we concentrate on the description of our annotation scheme for negotiation dialogues, illustrated with our pilot data, and some perspectives for future research on the issue

Volumetric optoacoustic neurobehavioral tracking of epileptic seizures in freely-swimming zebrafish larvae

Fast three-dimensional imaging of freely-swimming zebrafish is essential to understand the link between neuronal activity and behavioral changes during epileptic seizures. Studying the complex spatiotemporal patterns of neuronal activity at the whole-brain or -body level typically requires physical restraint, thus hindering the observation of unperturbed behavior. Here we report on real-time volumetric optoacoustic imaging of aberrant circular swimming activity and calcium transients in freely behaving zebrafish larvae, continuously covering their motion across an entire three-dimensional region. The high spatiotemporal resolution of the technique enables capturing ictal-like epileptic seizure events and quantifying their propagation speed, independently validated with simultaneous widefield fluorescence recordings. The work sets the stage for discerning functional interconnections between zebrafish behavior and neuronal activity for studying fundamental mechanisms of epilepsy and in vivo validation of treatment strategies

Conservation-compatible retrofit solutions in historic buildings: An integrated approach

Historic, listed, or unlisted, buildings account for 30% of the European building stock. Since they are complex systems of cultural, architectural, and identity value, they need particular attention to ensure that they are preserved, used, and managed over time in a sustainable way. This implies a demand for retrofit solutions able to improve indoor thermal conditions while reducing the use of energy sources and preserving the heritage significance. Often, however, the choice and implementation of retrofit solutions in historic buildings is limited by socio-technical barriers (regulations, lack of knowledge on the hygrothermal behaviour of built heritage, economic viability, etc.). This paper presents the approach devised in the IEA-SHC Task 59 project (Renovating Historic Buildings Towards Zero Energy) to support decision makers in selecting retrofit solutions, in accordance with the provision of the EN 16883:2017 standard. In particular, the method followed by the project partners to gather and assess compatible solutions for historic buildings retrofitting is presented. It focuses on best practices for walls, windows, HVAC systems, and solar technologies. This work demonstrates that well-balanced retrofit solutions can exist and can be evaluated case-by-case through detailed assessment criteria. As a main result, the paper encourages decision makers to opt for tailored energy retrofit to solve the conflict between conservation and energy performance requirements

Specific protein antigen delivery to human Langerhans cells in intact skin

Immune modulating therapies and vaccines are in high demand, not least to the recent global spread of SARS-CoV2. To achieve efficient activation of the immune system, professional antigen presenting cells have proven to be key coordinators of such responses. Especially targeted approaches, actively directing antigens to specialized dendritic cells, promise to be more effective and accompanied by reduced payload due to less off-target effects. Although antibody and glycan-based targeting of receptors on dendritic cells have been employed, these are often expensive and time-consuming to manufacture or lack sufficient specificity. Thus, we applied a small-molecule ligand that specifically binds Langerin, a hallmark receptor on Langerhans cells, conjugated to a model protein antigen. Via microneedle injection, this construct was intradermally administered into intact human skin explants, selectively loading Langerhans cells in the epidermis. The ligand-mediated cellular uptake outpaces protein degradation resulting in intact antigen delivery. Due to the pivotal role of Langerhans cells in induction of immune responses, this approach of antigen-targeting of tissue-resident immune cells offers a novel way to deliver highly effective vaccines with minimally invasive administration

The DisHuman child

In this paper we consider the relationship between the human and disability; with specific focus on the lives of disabled children and young people. We begin with an analysis of the close relationship between ‘the disabled’ and ‘the freak’. We demonstrate that the historical markings of disability as object of curiosity and register of fear serve to render disabled children as non-human and monstrous. We then consider how the human has been constituted, particularly in the periods of modernity and the rise of capitalism, reliant upon the naming of disability as antithetical to all that counts as human. In order to find a place for disabled children in a social and cultural context that has historically denied their humanity and cast them as monstrous others, we develop the theoretical notion of the DisHuman: a bifurcated complex that allows us recognise their humanity whilst also celebrating the ways in which disabled children reframe what it means to be human. We suggest that the lives of disabled children and young people demand us to think in ways that affirm the inherent humanness in their lives but also allow us to consider their disruptive potential: this is our DisHuman child. We draw on our research projects to explore three sites where the DisHuman child emerges in moments where sameness and difference, monstrosity/disability and humanity are invoked simultaneously. We explore three locations – (i) DisDevelopment; (ii) DisFamily and (iii) DisSexuality – illuminating the ways in which the DisHuman child seeks nuanced, politicized and complicating forms of humanity

Linear ubiquitin chain assembly complex coordinates late thymic T-cell differentiation and regulatory T-cell homeostasis.

The linear ubiquitin chain assembly complex (LUBAC) is essential for innate immunity in mice and humans, yet its role in adaptive immunity is unclear. Here we show that the LUBAC components HOIP, HOIL-1 and SHARPIN have essential roles in late thymocyte differentiation, FOXP3(+) regulatory T (Treg)-cell development and Treg cell homeostasis. LUBAC activity is not required to prevent TNF-induced apoptosis or necroptosis but is necessary for the transcriptional programme of the penultimate stage of thymocyte differentiation. Treg cell-specific ablation of HOIP causes severe Treg cell deficiency and lethal immune pathology, revealing an ongoing requirement of LUBAC activity for Treg cell homeostasis. These data reveal stage-specific requirements for LUBAC in coordinating the signals required for T-cell differentiation

How can the practice nurse be more involved in the care of the chronically ill? The perspectives of GPs, patients and practice nurses

BACKGROUND: A well established "midlevel" of patient care, such as nurse practitioners and/or physician assistants, exits in many countries like the US, Canada, and Australia. In Germany, however there is only one kind of profession assisting the physician in practices, the practice nurse. Little is known about the present involvement of practice nurses in patients' care in Germany and about the attitudes of GPs, assistants and patients concerning an increased involvement. The aim of our study was to get qualitative information on the extent to which practice nurses are currently involved in the treatment of patients and about possibilities of increased involvement as well as on barriers of increased involvement. METHODS: We performed qualitative, semi-structured interviews with 20 GPs, 20 practice nurses and 20 patients in the Heidelberg area. The interviews were digitally recorded, transcribed and content-analysed with ATLAS.ti. RESULTS: Practice nurses are only marginally involved in the treatment of patients. GPs as well as patients were very sceptical about increased involvement in care. Patients were sceptical about nurses' professional background and feared a worsening of the patient doctor relationship. GPs also complained about the nurses' deficient education concerning medical knowledge. They feared a lack of time as well as a missing reimbursement for the efforts of an increased involvement. Practice nurses were mostly willing to be more involved, regarding it as an appreciation of their role. Important barriers were lack of time, overload with administrative work, and a lack of professional knowledge. CONCLUSION: Practice nurses were only little involved in patient care. GPs were more sceptical than patients regarding an increased involvement. One possible area, accepted by all interviewed groups, was patient education as for instance dietary counselling. New treatment approaches as the chronic care model will require a team approach which currently only marginally exists in the German health care system. Better medical education of practice nurses is indispensable, but GPs also have to accept that they cannot fulfil the requirement of future care alone

Harnessing Naturally Occurring Tumor Immunity: A Clinical Vaccine Trial in Prostate Cancer

International audienceBACKGROUND:Studies of patients with paraneoplastic neurologic disorders (PND) have revealed that apoptotic tumor serves as a potential potent trigger for the initiation of naturally occurring tumor immunity. The purpose of this study was to assess the feasibility, safety, and immunogenicity of an apoptotic tumor-autologous dendritic cell (DC) vaccine.METHODS AND FINDINGS:We have modeled PND tumor immunity in a clinical trial in which apoptotic allogeneic prostate tumor cells were used to generate an apoptotic tumor-autologous dendritic cell vaccine. Twenty-four prostate cancer patients were immunized in a Phase I, randomized, single-blind, placebo-controlled study to assess the safety and immunogenicity of this vaccine. Vaccinations were safe and well tolerated. Importantly, we also found that the vaccine was immunogenic, inducing delayed type hypersensitivity (DTH) responses and CD4+ and CD8+ T cell proliferation, with no effect on FoxP3+ regulatory T cells. A statistically significant increase in T cell proliferation responses to prostate tumor cells in vitro (p = 0.002), decrease in prostate specific antigen (PSA) slope (p = 0.016), and a two-fold increase in PSA doubling time (p = 0.003) were identified when we compared data before and after vaccination.CONCLUSIONS:An apoptotic cancer cell vaccine modeled on naturally occurring tumor immune responses in PND patients provides a safe and immunogenic tumor vaccine