Chronic aortic aneurysms are permanent and localized dilations of the aorta that remain asymptomatic for long periods of time but continue to increase in diameter before they eventually rupture. Left untreated, the patients’ prognosis is dismal, since the internal bleeding of the rupture brings about sudden death. Although successful treatment cures the disease, the risky procedures can result in paraplegia from spinal cord ischaemia or even death, particularly for aneurysms extending from the thoracic to the abdominal aorta and thus involving many segmental arteries to the spinal cord, i.e. thoracoabdominal aortic aneurysms of Crawford type II. Although various strategies have achieved a remarkable decrease in the incidence of paraplegia, it is still no less than 10 to 20%. However, it has been found that the deliberate occlusion of the segmental arteries to the paraspinous collateral network finally supplying the spinal cord does not increase rates of permanent paraplegia. A therapeutic option, ‘minimally invasive segmental artery coil embolization’ has been devised which proceeds in a ‘staged’ way to occlude groups of arteries under highly controlled conditions after which time must be allowed for arteriogenesis to build a robust collateral blood supply. PAPA-ARTiS is a phase II trial to demonstrate that a staged treatment approach can reduce paraplegia and mortality dramatically. It can be expected to have both a dramatic impact on the individual patient's quality of life if saved from a wheelchair, and also upon financial systems through savings in; 1) lower costs in EU health care; 2) lower pay-outs in disability insurance (est. at 500k in Year 1), and; 3) loss of economic output from unemployment. Approx. 2500 patients a year in Europe undergo these high risk operations with a cumulative paraplegia rate of over 15%; therefore >100M per year in costs can be avoided and significantly more considering the expected elimination of type II endoleaks.

The CCHFVACIM project is an ambitious collaborative effort aimed at developing both prophylactic and therapeutic effective countermeasures against Crimean Congo Haemorrhagic Fever Virus (CCHFV), one of the most threatening vector-borne pathogens, widely distributed, including in the European continent. Deep structural biology studies on viral glycoproteins and investigation of the immunogenicity of the viral antigens will be combined with optimisation of an mRNA vaccine candidate against the virus and characterisation of the resulting protective immunity, as well as with the development of immunotherapeutic monoclonal antibodies (mAbs) based on CCHFV’s antigenic targets. To achieve the overarching goals, the CCHFVACIM project will build on the success of previous projects such as CCHFever (FP7), CCHFVaccine (H2020) and go the extra mile by initiating a unique One-Health platform strategy to address different aspects of this severe public health threat. On one hand, the project will use several advanced animal models (mice, sheep, and non-human primate) to assess and compare the efficacy of mRNA vaccine candidates, mAbs and therapeutic mRNA; on the other hand, it will establish a biobank from CCHF patients to build up a pipeline for the production of mAbs against CCHFV from their B cells. Importantly, the project will also contribute to capacity building of European infrastructures, with the establishment of a platform on mRNA-based vaccine at one of the partner institutions. Ultimately, CCHFVACIM will permit to develop a road map to bring the most efficacious vaccine candidates and immunotherapy tools to clinical trial Phase I in humans. The project results will be widely disseminated among the scientific community, public health authorities, non-governmental organisations, outbreak management teams, and hospitals, with the final scope of both contributing to contain the burden of CCHF disease and increasing preparedness to new outbreaks.

Our ability to remember past events and experiences lies at the core of cognition and behaviour. But how do fleeting moments get converted into durable memory traces? Recent work has highlighted the pivotal role of post-learning sleep for successful memory consolidation, the process of stabilising new memories over time. However, little is known about the neurophysiological mechanisms through which the sleeping brain consolidates new memories. Not only has this left a gap in our understanding of memory formation as a whole, but also the means to modulate memories during sleep have remained underexplored. SPIN will test the exciting hypothesis that particular electrophysiological signatures of sleep, namely sleep spindles, are the mechanistic vehicle driving memory consolidation. Specifically, I hypothesise that in coordination with hippocampal reactivation events, sleep spindles are deployed to cortical learning sites where they induce lasting structural changes. Using intracranial recordings from the human hippocampus (measuring single neuron firing and associated ‘ripple’ oscillations) and from an array of cortical areas, we will first establish whether spindles are temporally aligned with hippocampal reactivation events. Next, we will use high-density scalp EEG and functional as well as structural MRI in healthy participants to test whether spindle deployment to cortical learning sites predicts structural changes in these regions. To assert causality, we will examine the effects of invasive spindle perturbation in patients on memory consolidation. Finally, we will experimentally enhance local spindles to harness their potential as a tool for boosting human memory. In sum, SPIN will use an unprecedented array of human brain recording and stimulation techniques to provide a mechanistic link between learning, sleep and structural brain changes, culminating in novel tools to enhance human learning and memory.