Under the overarching theme, “United for Brain Innovation”, the Brain Innovation Days aim to bring together key opinion leaders and stakeholders from the ever-growing brain innovation ecosystem to create synergies and showcase the importance of brain innovation and how, one innovation at a time, it is changing Europe and the world.
Exhibition village
Organisations and Companies Featured
Book your seat
Platinum sponsor
Silver sponsors
EBC Members
Knowledge partners
Are you a company, funder/investor or start-up interested in supporting the Brain Innovation Days?
A number of sponsorship packages and add-on perks are available to choose from, including access to the programme, customised online content, exposure for your company/organisation and more.
BECOME PART OF THE BRAIN INNOVATION DAYS
Platinum sponsor
Silver sponsors
KNOWLEDGE PARTNERS
EBC Members
BECOME PART OF THE BRAIN INNOVATION DAYS
Are you a company, funder/investor or start-up interested in supporting the Brain Innovation Days?
A number of sponsorship packages and add-on perks are available to choose from, including access to the programme, customised online content, exposure for your company/organisation and more.
PARTNER Events
Researchers, start-ups, big pharma and beyond are all working tirelessly to provide innovative solutions. Want to learn more about the latest in the field? Read about the latest here.
Brain Talks is a weekly podcast a that invites key opinions leaders from the wider brain community to speak on exciting topics in the brain field, including neuroscience breakthroughs, leading innovations, policy-driven issues and creating successful start-ups.
An event organised by
Researchers, start-ups, big pharma and beyond are all working tirelessly to provide innovative solutions. Want to learn more about the latest in the field? Read about the latest here.
Brain Talks is a weekly podcast a that invites key opinions leaders from the wider brain community to speak on exciting topics in the brain field, including neuroscience breakthroughs, leading innovations, policy-driven issues and creating successful start-ups.
PITCHING SESSIONS
After careful analysis of over 90 applications from start-ups all over Europe, 9 finalists had a chance to impress the jury and the public by pitching their product or idea in 180 seconds during the second digital event held on 26 January 2021. We are very pleased to announce that PIPRA AG (short for Pre-Interventional Preventive Risk Assessment) became the winner of the 1st Brain Innovation Jury Award for Best Pitch. PIPRA AG is developing a cutting-edge AI-based pre-operative test to assess patient’s risk of suffering from cognitive disorders after a surgery. The 1st Brain Innovation Public Award for Best Pitch went to Icompanion, the digital companion for people with neurological conditions and their physicians.
Congratulations to our winners!
2 days of exciting events and multiple activities
Available to both physical and virtual audiences
Over 200 attendees expected from various expertises
Prominent, disruptive speakers in the field of brain research
An advanced meeting platform for one-on-one meetings
MATCHMAKING
The Brain Innovation Days stand out from other events as they put a large emphasis on networking and potential matchmaking within the community.
Acting as a catalyst for a community that can often be fragmented, the Brain Innovation Days, throughout the year, aim to create a hub – an extended community, of sorts – for maximum exposure for all attendees, connecting innovators with funders, researchers with start-ups and keen innovation partners, policymakers with the health & research communities and more.
Virtual launch event, exploring how brain innovation is changing Europe
Online panels, interviews and more with prominent speakers in their fields
“My Start-up in 180 seconds” Pitching Competition with an award for the ‘Best Pitch’
Matchmaking and networking opportunities
Online content streams with regular updates on the latest in brain innovation
The neurotech market as part of the neuroenhancement trend is rapidly growing and not shy of making big promises: consumer products for home use to boost attention, mood or memory. Gaining and maintaining the trust of consumers is paramount to succeeding in the neurotech market. However, in the scientific disciplines that form the foundation of these products – including Psychology, Neuroscience and Cognitive Science – concerns about the independent replication of research findings are acute. There is currently an evidence gap for both clinical and consumer product development – and filling this gap with trustworthy data requires robust research. Translational efforts in industry can therefore greatly benefit from robust and transparent research practices. Further, the call for responsible innovation and transparent R&D documentation is echoed by recent international policy updates of the European Medical Device Regulation and the U.S. Food and Drug Administration (FDA). Open science research practices seem to offer perfectly suited solutions to address these needs and reconcile innovation with robustness. Yet, their use is currently largely confined to academic communities. How can we close this knowledge gap efficiently and expedite the adoption of more robust research in the consumer market? We aim to engage with key stakeholders in the development of new neurotechnologies through:
Migraine is affected by 1 billion people worldside, 3 times more frequent in females, independent on race , culture and socioeconomic status. I wiil here describe my journey with CGRP from discovery to new medication. truely a 35 y period. At the end some recent thoughts on how hormones may be involved in the regulation of CGRP pathway.
Our session will explore four components of brain capital focused policy and investment innovations.
First, Dr. Harris Eyre will introduce brain capital. Brains are indispensable drivers of human progress. Why not invest more heavily in them? Dr. Eyre will talk about efforts to place brain capital at the center of a new narrative to fuel economic and societal recovery and resilience, along with efforts from the OECD Neuroscience-inspired Policy Initiative.
Second, Erin Smith will discuss women’s brain health innovations. The COVID-19 pandemic has exacerbated global mental health and gender inequalities. To improve women’s brain capital, we must incorporate new data: namely, the perspective and experience of women. Erin will discuss how solutions that consider the experience of women are more likely to create structural change across sectors, from neuroscience and health care to racial equality, public policy, and workplace norms.
Third, Dr. Caroline Montojo will talk about opportunities for public-private partnerships to advance neuroscience within society. Major national investments are being made into neuroscience research and neurotechnology development. New tools and technologies that carry strong ethical, legal, and social implications are rapidly touching upon the public sphere. Increased attention and investment into issues at the intersection of neuroscience and society will be critical. Dr. Montojo will discuss models for partnership between the public and private sectors to strengthen neuroscience’s role within society.
Fourth, Dr. Karen Rommelfanger will explore the competitive edge of neuroethics for neurotech innovators. The world is mobilizing around the allure of unlocking the mysteries of the brain from universities to healthcare and industry start-ups. Neurotechnology is rapidly developing to be applied in wide-ranging contexts. These advances in neuroscience continue to surface thorny ethical issues further complicated by diverse cultural assumptions about brain and mind. In this talk, Dr. Rommelfanger will discuss how neuroethics can be a creative tool to advance and accelerate the most societally impactful global neuroscience innovation.
This breakout session will give an in-depth look at the current state and future developments of EEG technology for daily use. Speakers from different backgrounds will present their (consumer) wearable EEG, clinical-grade wearable EEG and implantable EEG, augmented by an overview of the wealth of possibilities daily EEG would bring to people living with a brain disorder. In the first half of the session, each speaker will present the latest development in their field in about 10 minutes. Next, the session will continue with a moderated debate on the future of daily EEG and how this can impact people with a brain disorder.
It is estimated that one billion people worldwide live with migraine. The disease is three times more frequent in women, independent of race, culture and socioeconomic status. Prof. Edvinsson will describe his 35-year journey with calcitonin gene-related peptide (CGRP) from discovery to new medication. At the end of the Brain Talk, some recent thoughts on how hormone may be involved in the regulation of CGRP pathway will be shared.
Innovation is all around, also in Healthcare. In order to tackle the challenges, we’ll need an entrepreneurial mindset. What is that mindset? And why do startups sometimes succeed where others fail? In this session we’ll lift a tip of the veil on why startups matter and how organizations – both hospitals and corporates – can benefit from collaborating with them.
A social and innovative digital business leader with a critical and empathetic mindset, a lot of sense for responsibility and humor. And a touch of non-conformism. Loves the journey towards truly disruptive experiences by smart innovation and agility.
The workplace environment has a great impact on workers’ mental health and well-being, even more if considering the time people spend at work. A good psychosocial work environment can be very beneficial for workers’ mental health, whilst a poor one can have significant negative effects, including experiencing work-related stress, burnout, problems at home,drug and alcohol abuse. The negative effects impact the organizations too, that experience poor overall business performance, increased absenteeism, presenteeism and higher accident and injury rates.
This is the second most frequently reported work-related health problem in Europe, after musculoskeletal disorders.In the context of Industry 4.0, where robots, sensors and automated work are pervasive, conditions are potentially more harmful for workers’ mental health, as they could be exposed either to monotonous and alienating tasks or to very challenging tasks. The progressive adoption of collaborative robots (cobots) in manufacturing SMEs opens the way to a radical organizational and technological transformation, where by design the whole workplace environment could contribute to promote workers’ mental health.
The aim of our session is to show how an enhanced multi-stakeholder engagement takes into account manifold facets affecting mental health and intervenes on technological, relational and organizational aspects of the cobot-based work, fostering investment in research and innovation and facilitating SME business development.The objective is to design workplaces where level of challenge and difficulty of job tasks match with the workers’ abilities, in order to support their motivation and engagement by interacting with cobots in a flexible and personalized way. This will facilitate workers’ positive attitude, promoting good mental health and preventing negative experiences of anxiety or boredom and apathy that eventually lead to mental illnesses. Expected results are the definition of guidelines for the design of a “mental health friendly” manufacturing workplace and a new generation of cobots, the Mindbots.
Prior to the COVID-19 pandemic, the European Academy of Neurology had already decided to launch a taskforce on Gender and Diversity in Neurology, with the overall mission to increase awareness and improve knowledge about sex, gender, ethnic and racial differences and disparities in neurological disorders. Indeed, there are several biological, genetic, and epigenetic differences between men and women that can impact epidemiology, clinical manifestation, and treatment of many neurological disorders. Global burden ofneurological diseases affects much more women than men at any age.
Risk factors of stroke differs in women compare to men. Motor and non-motor fluctuations in Parkinson’s disease are not the same between men and women. Precision medicine in neurology needs neurologists to be aware of these differences to improve care and outcome of neurological patients. This session will provide new insights about this new expanding field of medicine applied to neurology.
What it takes to make Brain Pacemakers as routine as heart pacemakers and shifting the paradigm for Deep Brain Stimulation surgeries?
Similar to heart pacemakers, DBS is the gold standard for late-stage Parkinson’s treatment with world-wide regulatory approval, but adoption remains limited to ~5% due to patient access, procedure complexity, and cost, delaying and depriving eligible candidates. Diseases of cerebrovascular origins such as refractory hypertension, stroke, Alzheimer’s and vascular dementia rank alongside cancer as one of the greatest healthcare challenges faced by humanity, affecting one in three in later life.
Bioinduction has developed the first miniaturized precisely targeted, adaptive/responsive AI enabled, ‘brain-pacemaker’ called Picostim™, designed to be implanted directly into the skull and making it cosmetically invisible. Being a third of the size of conventional devices, it eliminates the need for tunneling extension wires (that need revision surgeries due to fractures) through neck tissue to a chest incision for the larger conventional batteries.
The elegant streamlined single-stage intra-operative skull integrated implantation workflow enables a safer, simpler, less traumatic, and less painful single-stage surgery, in less than half the time of conventional multi-stage, multi-day intervention, as well as doubling surgical productivity bringing cost savings for the health system, with lower life-cycle cost compared to conventional technologies. The procedure innovation harnesses convergence of state-of-the-art precise image guided planning and navigation enabling improved patient comfort with asleep surgery, an integrated surgical robot assistance, together delivering the future of brain pacemaker interventions.
Smart Picostim™ cranialized DBS platform innovation introduces a patient-centric brain pacemaker innovation together with an elegant single-stage procedure solution that enables paradigm change and introduces the future of brain pacemaker implantation to treat large unmet needs in chronic brain disorders via improved patient experience, increasing patient access, and improving overall outcomes for all the stakeholders.
Over the past decade we have demonstrated that the fusion of a patient’s own brain imaging data with computational dynamic models allows building personalized virtual brain models with diagnostic and prognostic performance. Our hybrid approach fuses data-driven with mechanistic modeling techniques and has been successfully applied in aging and stroke research and to clinical applications in epilepsy. Here we illustrate the workflow called Virtual Epileptic Patient (VEP) along the example of drug resistant epilepsy, where the application of machine learning and AI allows the estimation of the epileptogenic zone. A large multisite randomized clinical trial is testing VEP technology in epilepsy surgery patients. The workflow of end-to-end modeling is an integral part of the European neuroinformatics platform EBRAINS and enables neuroscientists worldwide to build and estimate personalized virtual brains. Virtual Brain Technologies (VB-Tech) has recently been created as a spin-off from AMU to exploit virtual brain technology with the mission of commercializing the VEP medical device as a trailblazer of TVB technology and the long-term vision of transversal extension to other diseases including Parkinson, multiple sclerosis, and Alzheimer. VB-Tech will address the market access challenge, for this technology and its future developments, transitioning from an academic prototype to an industrialized and certified medical device, allowing for the patients to benefit from it. VB-Tech will also be committed to adding a strong focus on medical education on top of the commercial objectives, placing the clinician in the center of the project.
Our objective is a drug correcting cognitive deficits in Alzheimer’s disease (AD). Our strategy is to use Down syndrome (DS) as a ‘back door’ to enter the AD therapeutic field. Cognitive deficits in AD and in DS can indeed be attributed to an excessive production/activity of the DYRK1A protein kinase (gene located on chromosome 21). Consequently, genetic and pharmacological inhibition of DYRK1A correct cognitive deficits in various animal models of AD and DS. These results have encouraged us to screen for, develop and optimize pharmacological inhibitors of DYRK1A for over 15 years. We discovered that Leucettamine B, a natural product extracted from the marine sponge Leucetta microraphis, inhibits DYRK1A with relatively good selectively. Inspired by this initial hit, we first synthesized, optimized and extensively characterized >500 analogues, the Leucettines. Improving the pharmacological properties of these compounds led us to Leucettinibs, a second-generation family of DYRK1A inhibitors (0.5-20 nM IC50, orally available, >560 compounds synthesized, 4 patents filed). Leucettines (ip) and Leucettinibs (p.o.) correct spatial and learning memory deficits observed in various animal models of AD and DS. This strong proof of concept (and data from other groups) supports the idea that pharmacological inhibition of DYRK1A might correct memory deficits in AD and DS patients. Our final clinical drug candidate, Leucettinib-21, was selected following a stringent GO/NO GO decision tree based on multiple in vitro and in vivo safety, pharmacology (ADMET) and IP parameters, strengthening our chance to develop a solid therapeutic drug candidate for the correction of cognitive deficits. The synthesis of a 1.5 kg, GLP batch of Leucettinib-21 is being carried for the regulatory preclinical studies which will start in January 2022.
Theoretical neuroscience suggests that consciousness depends on the ability of neural elements to engage in complex activity patterns that are, at once, distributed within a system of interacting cortical areas (integrated) and differentiated in space and time (information-rich) (i.e. brain complexity). Guided by this principle, we have been developing and testing empirical method to assess brain complexity based on a combination of transcranial magnetic stimulation (TMS) and electroencephalography (EEG). Overall, the estimation of brain complexity provides a reliable measuring scale along the unconsciousness/consciousness spectrum and allows a robust assessment of unresponsive individuals (such as locked-in, minimally conscious and vegetative state patients) whose level of consciousness cannot be assessed behaviorally. We are currently collaborating with a company (Nexstim, Finland) and other international partners to transform this strategy in a standardized clinical tool.
In 2017, more than 300 million people worldwide were estimated to suffer from brain disorders, imposing an economic burden of nearly 900 billion EUR in patient care. Therefore, the urgent need of the hour is to identify creative interventions to heal the brain and cure the mind. The goal of this breakout session is to bring together a world-leading group of panelists to discuss creative interventions and the interface of neuroscience and artificial intelligence to identify therapeutic treatments for brain disorders.
As an entrepreneur, there is a lot that is coming your way: While you’re developing your product and setting up your sales & marketing plan you also need to make sure you have the funds to execute your strategy and build a sustainable business. In this session, we will explore the different fundraising strategies (equity and non-equity) for start-ups.
We will go over pros & cons of different potential elements of the funding mix, take some time to dive deeper into the fundraising process and share some tips & tricks on how to prepare a solid story towards investors.
An interactive panel discussion where senior representatives from pharmaceutical companies will discuss their organizations areas of interest in neurology and psychiatry, their priorities for sponsored research, collaboration and partnering, criteria, and the approach to relationship development and collaboration. Special attention will be paid to challenges in the sector and addressing unmet medical needs. Questions from the audience will be encouraged.
An interactive panel discussion with senior representatives from large healthcare, technology and pharmaceutical companies. Discussion will focus on their application of imaging, Artificial Intelligence and digital technologies in the brain health space, their strategies and research and partnering interests. What are they developing internally and what are the priorities for external R&D and innovation partnering? In what areas are they keen to engage with partners, at what stage, and under what criteria? What areas are considered of greatest potential, and where are the most important challenges? Questions from the audience will be encouraged.
A discussion panel with leading European venture capital investors focused on or actively investing in CNS, neurology, psychiatry and brain related innovations, including both bio-pharma and imaging, AI, medtech and digital technologies. What are their specific investment interests, and why? What are their criteria, and at what stage do they engage and invest? How does this vary according to indication and approach? What data do they want to see and what other factors paly a key role in the decision to invest? How is risk assessed and managed, and are there greater barriers to investment in some areas of brain health than others, and why? Questions from the audience will be encouraged.
Amyotrophic lateral sclerosis (ALS) is a severe and fatal neurodegenerative disease characterized by an asymptomatic phase of undetermined duration while it takes on average about nine to 12 months for someone to be diagnosed with ALS. The time from the asymptomatic phase to the first notice of symptoms could last for years. However, there is no specific biomarker in the presympomatic phase, and there is no specific test for precise diagnostics in the symptomatic phase. At the early stages, ALS shows high clinical variability in presentation and prognosis and overlapping symptoms with other neurological disorders, so clinicians at that stage tend not to make such diagnosis. All of this leads to a diagnostic delay from several months to years causing progression of the disease that lead to complete patient disability and death without the possibility of successful treatment. Early, precise and more specific diagnosis is needed for adequate and personalized treatment.
We base our approach on decades of our pre-clinical research of ALS patient sera that led us to identify a set of novel biomarkers and a detection technology for early-stage ALS progression. We are developing a portable stand-alone clinical “lab on a chip”, NIMOCHIP® for disruptive in vitro diagnostics of ALS that could be further developed to diagnose other neurological disorders with an inflammatory component (e.g. multiple sclerosis, Parkinson’s disease, Alzheimer’s disease, Huntington’s disease,). NIMOCHIP® contains multiple chambers with seeded living cells (of animal or human – cell line origin) labeled with fluorescent probes, that are treated with nanoliter volumes of patient’s samples (purified immunoglobulins G – IgGs from patient sera).
NIMOCHIP is using “optics on a chip” technology that could measure a set of physiological fluorescence molecular biomarker signatures (intracellular calcium, reactive oxygen species – ROS, pH, ion channel responses). The acquired optical signals are analyzed using specialized software to obtain a personalized biomarker signature and to generate a detailed diagnostic report for the clinician.
The peer-review system for academic papers has a long yet quite conservative history. Yet, nowadays trends and changes in the speed of scientific processes are challenging the old peer-review system. Today, there is an increased need for speed to publish, yet scientists wish to maintain (at least the appearance of) the rigorous scientific quality of their results. This speed-quality trade-off results in several issues to be solved In my talk I will sketch out a new platform that aims to solve the above-mentioned challenges in a novel way. The idea is to provide a platform for neuroscientists working in the same field to start a study with peer-reviewed methods, upload and share their data and write together scientific papers. The peer-reviewed method would be beneficial for the quality of the research output while the data-sharing process could be beneficial for the pace of the publication process. The last part of the talk will be a brainstorming session about the possibilities of the platform. Feel free to contribute and get some ideas by checking scirec.org!
Walk With Path will present: “The use of smart insoles to improve gait and mobility in people with neurodegenerative conditions”. Our latest product in development, Path Feel, is a smart pressure-sensing insole which provides patented haptic feedback to the soles of the feet in response to pressure.
This improves sensory perception and proprioception by enhancing the sensation of the ground. Simultaneously, the insoles can analyse gait data to provide personalised care and empower users to take control back in their life via data-driven app and adjoining health care professional online dashboard. Walk With Path aims to understand how to incorporate wearables into care pathways to improve service provision, personalise care and provide tailored patient education.
Walk With Path mandates a patient-centred design process with the mission to improve the quality of life of people living with neurodegenerative conditions, with specific interest in stroke, multiple sclerosis and cerebral palsy populations.
Apart from the recording of electrical brain oscillations using EEG or MEG technology, optical radiation can be used to track cerebral blood flow and oxygenation as a measure of brain activity. Recent progress in sensor technology, miniaturisation, and user-friendliness have made optical brain imaging a scalable technology for D2C and clinical neurotech products. Yet, this technology has received less attention than EEG, where we have already seen a rise in D2C and clinical products on the market. Like EEG, optical brain imaging is easy to use and hardware can be produced at low cost, but it offers additional advantages: more precise localisation of brain activity and higher tolerance to user movements allow for a wider range of product use cases. With companies beginning to exploit these advantages, optical brain imaging is poised to shape the neurotech industry in the near future. This talk will be dedicated to this new trend. We highlight recent advancements in the field with views on applications, such as brain-computer interfaces and neurofeedback, and discuss the role of optical brain imaging in the brain innovation field. What can optical brain imaging already be used for today? What are the limitations? What are potential future applications and products?
Postoperative delirium (POD) affects 20% of surgical patients over the age of 60, making it the most prevalent post-surgical complication in older patients. It has severe adverse outcomes: doubles the risk of nursing home admissions, increases the risk of mortality by 25%, and often continues into long-term cognitive decline where 38% are still suffering nine months after surgery.
Once the symptoms of POD appear, it’s too late. The key to postoperative delirium is prevention, shown to decrease the incidence by 40%. This talk will present the results of a collaboration spanning 24 hospitals, two universities, and the start-up PIPRA addressing this urgent unmet need. Together, we developed an AI-based software able to identify patients at risk before surgery, allowing for preventive measures to be taken.
Are you a policymaker, clinician, researcher, investor or brain health enthusiast? Join this talk to hear what can be done today and how you can help prevent POD.
With the increased access to easy-to-use neurostimulation devices for home use, in combination with an increased datastream from users physical and cognitive behaviour, how can we best combine the two to create new cognitive treatment paradigms?
The recent advances in Information and Communication Technologies (ICTs) enabled a growing amount of people worldwide to remotely interact at affordable costs, embracing the possibility to join in complex human activities like neurorehabilitation. During the last decades telemedicine tools have been implemented, which have proven to be a solution for continuity of care in patients at risk of isolation (e.g. people living in remote areas worldwide) and in several clinical conditions (e.g. immunocompromised individuals) showing good adherence and also a positive impact in terms of efficacy in different areas of intervention. Additionally, telerehabilitation can be adapted to multiple clinical conditions and allows individualization of treatment to suit the needs of the patient and the pathology.
The health pandemic caused by SARS-CoV-2 (COVID-19) has limited the access of a large number of patients with acquired brain damage to neurorehabilitation programs [1]. The activities of the rehabilitative team were limited to those strictly necessary: the out-patients’ treatments or those delivered at home by therapists were suspended ante most of in-patients were confined to patient’s room. Noteworthy, beyond physical distancing measures, also changes in healthcare services access regulation are negatively affecting the access to rehabilitative services during the current pandemic [2].
Ensuring the continuity of cure, an adequate treatment intensity and repetition over time are major challenges in neurorehabilitation. Telerehabilitation can potentially enable continuum of care in situations of physical distancing, so it could be an effective alternative to physical intervention and mitigate some negative effects caused by the pandemic. As far as neurorehabilitation is concerned, most of the programmes developed have focused on specific aspects, especially motor aspects such as balance or upper limb, but not on a multi-specialist approach or within a more global framework. Moreover, most of these studies have used selected samples with restricted inclusion criteria (excluding cognitive problems, language, major dependencies…).
The objective of this study was to determine the effectiveness, adherence and usability of a teleneurorehabilitation tool aimed at providing patients with acquired brain injury with clinical assistance during the pandemic.
Methods
All patients older than 18 years old who participated in a face-to-face neurorehabilitation program at the time of confinement were candidates to participate in a teleneurorehabilitation program. An individual intervention was planned for all the participants who accepted to participate in the teleneurorehabilitation program to replicate their face-to-face program, reproducing the contents, duration and frequency of the sessions, as well as their previously assigned therapists. This planning was reviewed weekly. The effectiveness of the program was determined from the change in functional independence, determined with the extended version of the Barthel Index, once the face-to-face activity was resumed. The adherence to the program was assessed by the responsible therapist using a 10-point Likert scale. The usability of the teleneurorehabilitation tool was determined by the participants using an “ad-hoc” questionnaire.
Conclusions
The teleneurorehabilitation intervention was effective at improving the independence of patients with acquired brain injury, and promoted high adherence and usability. These data could be seen as an opportunity to rethink current neurorehabilitative routines, envisioning mixed procedures in which face-to-face sessions are integrated and combined with telerehabilitation.
