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International audience; Objective: Dysfunction of social cognition is well-recognized as one of amyotrophic lateral sclerosis (ALS) cognitive impairments. Previous studies have mostly associated social cognition subcomponents, including Theory of Mind (ToM), with executive dysfunction using highlydemanding tasks. In the present study, we investigate dysfunction of affective ToM in a sample of ALS patients without dementia and evaluate any possible associations both with executive and non-executive dysfunction. Methods: We included 42 ALS patients and 30 healthy controls (HC) and administered the Edinburgh Cognitive and Behavioural Amyotrophic Lateral Sclerosis Screen (ECAS). Affective ToM was examined based on the ECAS judgment of preference task; total score and type of errors ("favourite", "unclassified") were recorded for all participants. Results: A significant proportion of ALS patients (31%) were impaired on ToM task, scoring significantly lower compared to HC. Impairments in ToM task were more frequent (45%) in patients with cognitive impairment compared to those with intact cognition (15%). ALS patients showed significantly more errors on ToM task compared to HC. A significant association was found between ToM score and ECAS language and visuospatial abilities but not fluency, executive or memory function. Conclusion: Dysfunction of affective ToM appears prevalent in ALS patients without dementia, and associates with language and visuospatial abilities. These associations align with motor and extra-motor symptoms due to the degeneration across corresponding networks. Impaired ToM should be considered in clinical settings, since it might contribute to patients' social life, as well as the burden of their caregivers and relatives.

Recent research has focused on assessing either event- or time-based prospective memory (PM) using laboratory tasks. Yet, the findings pertaining to PM performance on laboratory tasks are often inconsistent with the findings on corresponding naturalistic experiments. Ecologically valid neuropsychological tasks resemble the complexity and cognitive demands of everyday tasks, offer an adequate level of experimental control, and allow a generalisation of the findings to everyday performance. The Virtual Reality Everyday Assessment Lab (VR-EAL), an immersive virtual reality neuropsychological battery with enhanced ecological validity, was implemented to comprehensively assess everyday PM (i.e., focal and non-focal event-based, and time-based). The effects of the length of delay between encoding and initiating the PM intention and the type of PM task on everyday PM performance were examined. The results revealed that everyday PM performance was affected by the length of delay rather than the type of PM task. The effect of the length of delay differentially affected performance on the focal, non-focal, and time-based tasks and was proportional to the PM cue focality (i.e., semantic relationship with the intended action). This study also highlighted methodological considerations such as the differentiation between functioning and ability, distinction of cue attributes, and the necessity of ecological validity., Comment: 9 Figures, 4 Tables

Myotonic dystrophies (DMs) are hereditary, multisystem, slowly progressive myopathies. One of the systems they affect is the CNS. In contrast to the well-established cognitive profile of myotonic dystrophy type 1 (DM1), only a few studies have investigated cognitive dysfunction in individuals with myotonic dystrophy type 2 (DM2), and their findings have been inconsistent. To identify the most commonly affected cognitive domains in individuals with DM2, we performed a formal comprehensive review of published DM2 studies. Using the terms "myotonic dystrophy type 2" AND "cognitive deficits," "cognitive," "cognition," "neuropsychological," "neurocognitive," and "neurobehavioral" in all fields, we conducted an advanced search on PubMed. We read and evaluated all of the available original research articles (13) and one case study, 14 in total, and included them in our review. Most of the research studies of DM2 reported primary cognitive deficits in executive functions (dysexecutive syndrome), memory (short-term nonverbal, verbal episodic memory), visuospatial/constructive-motor functions, and attention and processing speed; language was rarely reported to be affected. Based on the few neuroimaging and/or multimodal DM2 studies we could find, the cognitive profile of DM2 is associated with brain abnormalities in several secondary and high-order cortical and subcortical regions and associative white matter tracts. The limited sample size of individuals with DM2 was the most prominent limitation of these studies. The multifaceted profile of cognitive deficits found in individuals with DM2 highlights the need for routine neuropsychological assessment at both baseline and follow-up, which could unveil these individuals' cognitive strengths and deficits.

In this PhD, a technological systematic literature review of the reasons for adverse symptomatology was conducted and suggestions and technological knowledge for the implementation of virtual reality HMD systems in cognitive neuroscience provided. Another aim of this PhD was to devise a brief tool to appraise and report both the quality of software features and VRISE intensity quantitatively; such a tool does not currently exist. The Virtual Reality Neuroscience Questionnaire (VRNQ; Kourtesis et al., 2019) was developed to assess the quality of virtual reality software in terms of user experience, game mechanics, in-game assistance, and VRISE. The results demonstrated that VRNQ is a valid tool for assessing virtual reality software as it has good convergent, discriminant, and construct validity. The maximum duration of virtual reality sessions should be between 55 and 70 min when the virtual reality software meets or exceeds the parsimonious cut-offs of the VRNQ, and the users are familiarized with the virtual reality system. The VRNQ facilitates the brief assessment and reporting of the quality of virtual reality software features and/or the intensity of VRISE, while its minimum and parsimonious cut-offs may appraise the suitability of virtual reality software for implementation in research and clinical settings. However, the development of virtual reality software is predominantly dependent on third parties (e.g., freelancers or companies) with programming and software development skills. In Chapter 4, guidelines are offered for the development of virtual reality software in cognitive neuroscience and neuropsychology, by describing and discussing the stages of the development of Virtual Reality Everyday Assessment Lab (VR-EAL), the first neuropsychological battery in immersive virtual reality. Techniques for evaluating cognitive functions within a realistic storyline are discussed. The utility of various assets in Unity, software development kits, and other software are described so that cognitive scientists can overcome challenges pertinent to VRISE and the quality of the virtual reality software. The virtual reality neuroscience questionnaire (VRNQ) was implemented to appraise the quality of the three versions of VR-EAL in terms of user experience, game mechanics, in-game assistance, and VRISE. The final version of VR-EAL achieved high scores in every sub-score of the VRNQ and exceeded its parsimonious cut-offs. The results substantially support the feasibility of the development of effective virtual reality research and clinical software without the presence of VRISE during a 60-min virtual reality session. In Chapter 5, validation of VR-EAL as an assessment of prospective memory, episodic memory, attention, and executive functions using an ecologically valid approach is examined. Performance on the VR-EAL, an immersive virtual reality neuropsychological battery, is examined against an extensive paper-and-pencil neuropsychological battery. VR-EAL scores were significantly correlated with their equivalent scores on the paper-and-pencil tests. The participants' reports indicated that the VR-EAL tasks were considered significantly more ecologically valid and pleasant than the paper-and-pencil neuropsychological battery. The VR-EAL battery also had a shorter administration time. The VR-EAL appears to be an effective neuropsychological tool for the assessment of everyday cognitive functions, and has enhanced ecological validity, a highly pleasant testing experience, and does not induce cybersickness. In the final part of this thesis, the preparatory attentional and memory (PAM) and the multiprocess theories of prospective memory are examined by attempting to identify the cognitive functions which may predict the individual's performance on ecologically valid prospective memory tasks in the same group of participants described in Chapter 5. The results revealed that the type of prospective memory task does not play a significant role in everyday prospective memory functioning, but instead the length of delay between encoding and retrieving the prospective memory intention plays a central role. Support for the PAM and MP frameworks was found in non-focal and focal event-based tasks respectively. However, the findings, inferring a dynamic interplay between automatic and intentional monitoring and retrieval processes, agree with the inclusive approach of the multiprocess framework. Also, the role of executive functions appears crucial in everyday PM. Finally, everyday PM is predominantly facilitated by episodic memory, visuospatial attention, auditory attention, and executive functions. In conclusion, this PhD thesis attempted to show how immersive virtual reality research methods may be implemented efficiently without the confounding effect of cybersickness symptomatology in order to enhance the ecological validity of neuropsychological testing and contribute to our understanding of everyday cognitive ability.

Background: Digital technologies are creating unprecedented opportunities to improve and increase support to older people with cognitive and mental health problems, and to their family and carers. However, barriers that preclude the implementation of technology driven programs for the assessment and intervention of adults at risk of cognitive decline need to be better understood. This study investigated these outstanding issues, as well as considering the impact that the COVID-19 Pandemic has had on such barriers.Methods: A sample of 105 participants completed an online survey. Their ages ranged from 18 to 92 years. Of these,72%were female,83%had higher education and beyond, 42% were working, 42% were retired, and 14% were unemployed. The questionnaires assessed IT experience alongside awareness, attitudes, and stigmas regarding the use of technologies, particularly those used to support cognitive and mental health. Questionnaires also explored the impact of the COVID-19 pandemic on these technology-related factors. We compared these across groups of young (n=45), middle age (n=12) and older adults (n=48).Results: Relative to younger participants, older participants were less aware of, and held stronger stigmas against healthcare technologies, even though they reported more IT experience. IT awareness was associated to more positive (r=0.619, p

In contrast to myotonic dystrophy type 1, the cognitive and radiologic profile of myotonic dystrophy type 2 (DM2) is relatively poorly characterized.To conduct a pilot study to systematically evaluate cognitive and radiologic features in a cohort of Greek individuals with DM2.Eleven genetically confirmed individuals with DM2 and 26 age- and education-matched healthy controls were administered the Edinburgh Cognitive and Behavioural Amyotrophic Lateral Sclerosis Screen (ECAS) to screen for impairment in multiple cognitive domains. MRI data were evaluated by morphometric analyses to identify disease-specific gray and white matter alterations. The following statistical thresholds were used for cognitive comparisons: PFDR0.05 and Bayes factor (BF 10 )10.The DM2 group exhibited cognitive impairment (ECAS Total score; PFDR = 0.001; BF 10 = 108.887), which was dominated by executive impairment ( PFDR = 0.003; BF 10 = 25.330). A trend toward verbal fluency impairment was also identified. No significant impairments in memory, language, or visuospatial function were captured. The analysis of subscores revealed severe impairments in social cognition and alternation. Voxel-based morphometry identified widespread frontal, occipital, and subcortical gray matter atrophy, including the left superior medial frontal gyrus, right medial orbitofrontal gyrus, right operculum, right precuneus, bilateral fusiform gyri, and bilateral thalami.DM2 may be associated with multifocal cortical and thalamic atrophy, which is likely to underpin the range of cognitive manifestations mostly characterized by executive impairment and specifically by impaired social cognition.

Clinical tools involving immersive virtual reality (VR) may bring several advantages to cognitive neuroscience and neuropsychology. However, there are some technical and methodological pitfalls. The American Academy of Clinical Neuropsychology (AACN) and the National Academy of Neuropsychology (NAN) raised 8 key issues pertaining to Computerized Neuropsychological Assessment Devices. These issues pertain to: (1) the safety and effectivity; (2) the identity of the end-user; (3) the technical hardware and software features; (4) privacy and data security; (5) the psychometric properties; (6) examinee issues; (7) the use of reporting services; and (8) the reliability of the responses and results. The VR Everyday Assessment Lab (VR-EAL) is the first immersive VR neuropsychological battery with enhanced ecological validity for the assessment of everyday cognitive functions by offering a pleasant testing experience without inducing cybersickness. The VR-EAL meets the criteria of the NAN and AACN, addresses the methodological pitfalls, and brings advantages for neuropsychological testing. However, there are still shortcomings of the VR-EAL, which should be addressed. Future iterations should strive to improve the embodiment illusion in VR-EAL and the creation of an open access VR software library should be attempted. The discussed studies demonstrate the utility of VR methods in cognitive neuroscience and neuropsychology.

Haptic feedback is critical in a broad range of human-machine/computer-interaction applications. However, the high cost and low portability/wearability of haptic devices remains an unresolved issue, severely limiting the adoption of this otherwise promising technology. Electrotactile interfaces have the advantage of being more portable and wearable due to its reduced actuators’ size, as well as benefiting from lower power consumption and manufacturing cost. The usages of electrotactile feedback have been explored in human-computer interaction and human machine-interaction for facilitating hand-based interactions in applications such as prosthetics, virtual reality, robotic teleoperation, surface haptics, portable devices, and rehabilitation. This paper presents a systematic review and meta-analysis of electrotactile feedback systems for hand based interactions in the last decade. We categorize the different electrotactile systems according to their type of stimulation and implementation/application. We also present and discuss a quantitative congregation of the findings, so as to offer a high-level overview into the state-of-art and suggest future directions. Electrotactile feedback was successful in rendering and/or augmenting most tactile sensations, eliciting perceptual processes, and improving performance in many scenarios, especially in those where the wearability/portability of the system is important. However, knowledge gaps, technical drawbacks, and methodological limitations were detected, which should be addressed in future studies.

Studies on prospective memory (PM) predominantly assess either event- or time-based PM by implementing non-ecological laboratory-based tasks. The results deriving from these paradigms have provided findings that are discrepant with ecologically valid research paradigms that converge on the complexity and cognitive demands of everyday tasks. The Virtual Reality Everyday Assessment Lab (VR-EAL), an immersive virtual reality (VR) neuropsychological battery with enhanced ecological validity, was implemented to assess everyday event- and time-based PM, as well as the influence of other cognitive functions on everyday PM functioning. The results demonstrated the importance of delayed recognition, planning, and visuospatial attention on everyday PM. Delayed recognition and planning ability were found to be central in event- and time-based PM respectively. In order of importance, delayed recognition, visuospatial attention speed, and planning ability were found to be involved in event-based PM functioning. Comparably, planning, visuospatial attention accuracy, delayed recognition, and multitasking/task-shifting ability were found to be involved in time-based PM functioning. These findings further suggest the importance of ecological validity in the study of PM, which may be achieved using immersive VR paradigms., Comment: 4 Figures , 4 Tables. arXiv admin note: text overlap with arXiv:2102.10448

Objective:This study aimed to adapt the Addenbrooke’s Cognitive Examination-III (ACE-III) and Mini-Addenbrooke’s Cognitive Examination (M-ACE) into Greek and then to examine the convergent validity against their predecessors Addenbrooke’s Cognitive Examination-Revised (ACE-R) and Mini-Mental State Examination (MMSE) in a Greek population. Moreover, a primary aim was to appraise the utility of each screen by conducting a comparison of the psychometric properties of ACE-III, M-ACE, ACE-R, MMSE, and the Edinburgh Cognitive and Behavioural Amyotrophic Lateral Sclerosis (ALS) Screen (ECAS) in detecting Alzheimer’s disease (AD).Methods:Forty patients with AD were recruited and matched with 38 controls. Bayesian Pearson’s correlation analysis was conducted to examine the convergent validity. Receiver operating characteristic curve analysis was implemented to appraise the sensitivity and specificity of the tests in detecting AD.Results:The ACE-III, M-ACE, and the ECAS scores robustly correlated with ACE-R and MMSE. The ACE-III and the ECAS-ALS Non-Specific score were the most sensitive and specific tools in detecting AD, closely followed by ECAS Total score and M-ACE. Only ECAS Total score correlated with the duration of disease. The ECAS scores were more resilient to ceiling effects than the other screens. M-ACE produced fewer ceiling effects than MMSE.Conclusion:The Greek ACE-III and M-ACE were successfully adapted and showed good convergent validity against their predecessors. They showed very good psychometric properties in detecting AD and may be considered in hectic clinical settings. ECAS Total score and ECAS-ALS Non-Specific showed comparable psychometric properties in the detection of AD and may be considered in polypathological clinics where motor impairments are common.

Introduction/Background The immune checkpoints NKG2A and programmed cell death-1 (PD-1) are expressed on both tumour-infiltrating natural killer (NK) and CD8+ T cells in several cancer types, and are implicated in reducing antitumor immune response. To evaluate whether dual targeting of non-redundant checkpoint pathways (NKG2A/HLA-E and PD-1/PD-L1) may enhance antitumour immunity, the combination of monalizumab and durvalumab is being assessed in a Phase 1b expansion study in multiple solid tumours (NCT02671435). Here we report safety and efficacy results in patients with ovarian, cervical or microsatellite-stable (MSS) endometrial cancer. Methodology Eligible patients had advanced recurrent or metastatic high-grade serous epithelial ovarian cancer or cervical cancer (patients in each cohort could have received up to 2 prior lines of systemic therapy) or MSS endometrial cancer (patients could have received up to 3 prior lines of systemic therapy), with Eastern Cooperative Oncology Group performance status 0–1. Patients received monalizumab 750 mg Q2W and durvalumab 1500 mg Q4W for up to 3 years until unacceptable toxicity or confirmed progression. The primary endpoint was safety and tolerability; secondary endpoints included antitumour activity. Results Between March 2017 and March 2019, 40 patients with ovarian cancer (age range, 42–75 years), 16 patients with cervical cancer (age range, 32–79 years) and 40 patients with MSS endometrial cancer (age range, 45–79 years) were enrolled. Rates of treatment-related adverse events (AEs) were generally similar across cohorts (table 1). There were no grade 5 AEs and no events leading to discontinuation of monalizumab or durvalumab. Objective responses were seen only in ovarian cancer (table 2): among the 37 evaluable patients, 2 (5.4%) had confirmed partial responses and 10 (27.0%) had stable disease (SD) including 6 (16.2%) with disease control at 24 weeks (DCR24). Median progression-free survival (mPFS) was 1.8 months and median overall survival (mOS) was 16.7 months. Six (37.5%) of the 16 evaluable patients with cervical cancer had SD; mPFS was 2.0 months and mOS was 8.6 months. Fifteen (38.5%) of the 39 evaluable patients with MSS endometrial cancer had SD, including 5 (12.8%) with DCR24; mPFS was 1.8 months and mOS was 10.7 months. Conclusion Monalizumab plus durvalumab treatment had manageable safety in all cohorts. Modest clinical activity was demonstrated in recurrent ovarian cancer, whereas activity in cervical and MSS endometrial cancers was minimal. Further understanding of dual immune-checkpoint targeting is required. Disclosures Susana Banerjee has received institution research grants from AstraZeneca, Tesaro, and GlaxoSmithKline, and honoraria for advisory boards/lectures from AstraZeneca, Amgen, Clovis, Genmab, GlaxoSmithKline, Immunogen, Mersana, Merck Serono, Merck Sharp & Dohme, Pfizer, Roche, Seattle Genetics, and Tesaro. Ana Oaknin has served on advisory boards for Clovis Oncology, AstraZeneca, Genmab/Seattle Genetics, ImmunoGen, PharmaMar, Roche, GSK/Tesaro, Merck/Merck Sharp & Dohme, Deciphera and Mersana; has received support for travel or accommodation from Clovis Oncology, AstraZeneca, PharmaMar, and Roche; and reports institutional research grant support from Clovis Oncology, AbbVie Deutschland, Ability Pharmaceuticals, Advaxis, Aeterna Zentaris, Amgen, Aprea Therapeutics, Eisai, ImmunoGen, Merck/Merck Sharp & Dohme, Millennium Pharmaceuticals, PharmaMar, Roche, and Tesaro. IS-S: No conflicts to disclose ACS: No conflicts to disclose Sandip Pravin Patel receives scientific advisory income from AstraZeneca, Bristol Myers Squibb, Eli Lilly, Illumina, Rakuten, Paradigm and Tempus, and research funding from Bristol Myers Squibb, Eli Lilly, Incyte, AstraZeneca, Merck, Pfizer, Roche/Genentech, Xcovery, Fate Therapeutics, Genocea and Iovance. AOz: No conflicts to disclose Mayukh Das is an employee of and stockholder in AstraZeneca. Panagiotis Kourtesis is an employee of and stockholder in AstraZeneca. Maria Libera Ascierto is an employee of and stockholder in AstraZeneca. Jennifer R. Diamond reports research funding from AstraZeneca, Immunomedics, OnKure, Bristol Myers Squibb, Merck, Deciphera, Bayer, Taiho and Takeda and consulting work for Immunomedics.

Objectives: 1) Adapt the ECAS into Greek, validate it in ALS patients and compare with the ALS-CBS 2) Determine the sensitivity and specificity of ECAS in the differentiation between AD and non-demented ALS patients as compared with the ACE-III and mini-ACE. Methods: ALS patients (n=28) were recruited. and AD patients (n=26) matched in age, sex, and education with ALS patients (n=24). The normative data was derived from a random sample of controls (n=52). Bayes correlation analysis was conducted to examine convergent validity. Bayes t-test was performed to assess between groups’ differences. Receiver operating characteristics (ROC) curve analyses and area under the curve (AUC) were implemented to appraise the sensitivity and specificity in the differentiation between AD and non-demented ALS patients. Results: The ECAS and its sub-scores in addition to the behaviour interview demonstrated robust correlations with the ALS-CBS. Impairment in language and verbal fluency were the most prominent deficits in the ALS patients. The most frequently reported change was apathy. The ROC analysis demonstrated that the ECAS-ALS Non-Specific score (comprising memory and visuospatial domains) is the most sensitive and specific in differentiating AD from ALS patients. The other measures expressed high sensitivity, yet a poor specificity. Conclusions: The ECAS is a multi-purpose screening tool. The ECAS-ALS Specific appraises the whole spectrum of the highly prevalent cognitive impairments in ALS. The ECAS-ALS Non-Specific (memory and visuospatial) is a sensitive score to detect AD related deficits and is able to differentiate AD from non-demented ALS patients better than the ACE-III and mini-ACE

Myotonic dystrophies (DMs) are hereditary, multisystem, slowly progressive myopathies. One of the systems they affect is the CNS. In contrast to the well-established cognitive profile of myotonic dystrophy type 1 (DM1), only a few studies have investigated cognitive dysfunction in individuals with myotonic dystrophy type 2 (DM2), and their findings have been inconsistent. To identify the most commonly affected cognitive domains in individuals with DM2, we performed a formal comprehensive review of published DM2 studies. Using the terms "myotonic dystrophy type 2" AND "cognitive deficits," "cognitive," "cognition," "neuropsychological," "neurocognitive," and "neurobehavioral" in all fields, we conducted an advanced search on PubMed. We read and evaluated all of the available original research articles (13) and one case study, 14 in total, and included them in our review. Most of the research studies of DM2 reported primary cognitive deficits in executive functions (dysexecutive syndrome), memory (short-term nonverbal, verbal episodic memory), visuospatial/constructive-motor functions, and attention and processing speed; language was rarely reported to be affected. Based on the few neuroimaging and/or multimodal DM2 studies we could find, the cognitive profile of DM2 is associated with brain abnormalities in several secondary and high-order cortical and subcortical regions and associative white matter tracts. The limited sample size of individuals with DM2 was the most prominent limitation of these studies. The multifaceted profile of cognitive deficits found in individuals with DM2 highlights the need for routine neuropsychological assessment at both baseline and follow-up, which could unveil these individuals' cognitive strengths and deficits.

Background Immune checkpoint inhibitors have shown limited clinical benefits in MSS-CRC; dual targeting of non-redundant pathways may enhance antitumor immune response. In a phase I/II, multicenter, open-label study, the anti-PD-L1 antibody durvalumab (D) was combined with monalizumab (M), an IgG4 mAb that blocks NKG2A binding to HLA-E to reduce inhibition of NK and CD8+ T cells. The combination (D+M) was well tolerated and showed encouraging activity in heavily pretreated pts with advanced MSS-CRC. In a dose-exploration cohort, D+M was assessed in combination with standard of care (SOC) chemotherapy and bevacizumab, an anti-VEGF agent, as first-line therapy for advanced/metastatic MSS-CRC. Methods Eligible pts had histologically defined MSS-CRC, regardless of RAS/RAF mutational status, ECOG 0–1 and no prior systemic therapy. They received durvalumab 1500mg Q4W, monalizumab 750mg Q2W, modified FOLFOX6 (folinic acid, fluorouracil, and oxaliplatin) Q2W and bevacizumab 5mg/kg Q2W until end of treatment; dose modifications were allowed according to SOC practice except during the DLT evaluation period. The primary endpoint was safety and tolerability of D+M with FOLFOX6 and bevacizumab; secondary endpoints included antitumor activity. Results As of Mar 25, 2019, 18 pts were enrolled with median follow-up of 6.2 months. Monalizumab-related adverse events (AEs) occurred in 13 (72%), serious in 1 (6%; embolism). Durvalumab-related AEs occurred in 14 (78%; none serious). All pts had chemotherapy-related AEs, serious in 1 (6%; febrile neutropenia) and 10 (56%) had bevacizumab-related AEs, serious in 2 (11%; embolism and febrile neutropenia). There were no grade 5 or dose-limiting toxicities. At 16 weeks, 17 pts were evaluable for response; 9 (53%) had partial responses (7 confirmed, 2 unconfirmed), 6 (35%) had stable disease and 2 (12%) had progressive disease; there were no complete responses. Median time to response for the 7 confirmed responders was 15.4 weeks; median duration of response was not yet reached. Conclusions First-line D+M combined with SOC showed manageable safety and preliminary activity in pts with advanced/metastatic MSS-CRC. Accrual is complete. Clinical trial identification NCT02671435. Editorial acknowledgement Medical writing support was provided by Hashem Dbouk, PhD, of Cirrus Communications (Lyndhurst, NJ), an Ashfield company, and was funded by AstraZeneca. Legal entity responsible for the study AstraZeneca. Funding AstraZeneca. Disclosure J.C. Bendell: Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Gilead; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Genentech/Roche; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; Advisory / Consultancy, Research grant / Funding (institution): Five Prime; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Lilly; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Merck; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Celgene; Research grant / Funding (institution): EMD Serono; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Taiho; 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Research grant / Funding (institution): Forty Seven; Research grant / Funding (institution): AbbVie; Advisory / Consultancy, Research grant / Funding (institution): Array; Research grant / Funding (institution): Onyx; Advisory / Consultancy, Research grant / Funding (institution): Sanofi; Research grant / Funding (institution): Takeda; Research grant / Funding (institution): Eisai; Research grant / Funding (institution): Celldex; Advisory / Consultancy, Research grant / Funding (institution): Agios; Research grant / Funding (institution): Cytomx; Research grant / Funding (institution): Nektar; Research grant / Funding (institution), Travel / Accommodation / Expenses: ARMO; Research grant / Funding (institution): Boston Biomedical; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Ipsen; Advisory / Consultancy, Research grant / Funding (institution): Merrimack; Research grant / Funding (institution): Tarveda; Research grant / Funding (institution): Tyrogenex; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Oncogenex; Research grant / Funding (institution): Marshall Edwards; Research grant / Funding (institution): Pieris; Research grant / Funding (institution): Mersana; Research grant / Funding (institution): Calithera; Research grant / Funding (institution): Blueprint; Research grant / Funding (institution): Evelo; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Forma; Research grant / Funding (institution): Merus; Research grant / Funding (institution): Jacobio; Research grant / Funding (institution): Effector; Research grant / Funding (institution): Novocare; Research grant / Funding (institution): Arrys; Research grant / Funding (institution): Tracon; Research grant / Funding (institution): Sierra; Advisory / Consultancy, Research grant / Funding (institution): Innate; Advisory / Consultancy, Research grant / Funding (institution): Arch Oncology; 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Advisory / Consultancy: Moderna Therapeutics; Advisory / Consultancy: Tanabe Research Laboratories; Advisory / Consultancy: Beigene; Advisory / Consultancy: Continuum Clinical; Advisory / Consultancy: Kyn. J. Naidoo: Research grant / Funding (institution): Merck; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy: BMS. X. Li: Full / Part-time employment: AstraZeneca. P. Kourtesis: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. S.E. Abdullah: Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. S. Patel: Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy: Illumina; Advisory / Consultancy: Nektar; Advisory / Consultancy: Tempus; Research grant / Funding (institution): Eli Lilly; Research grant / Funding (institution): Fate; Research grant / Funding (institution): Incyte; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Roche/Genentech; Research grant / Funding (institution): Xcovery; Research grant / Funding (institution): Fate Therapeutics; Research grant / Funding (institution): Genocea; Research grant / Funding (institution): Iovance. All other authors have declared no conflicts of interest.

The Protein Information Resource (PIR) is an integrated public resource of protein informatics. To facilitate the sensible propagation and standardization of protein annotation and the systematic detection of annotation errors, PIR has extended its superfamily concept and developed the SuperFamily (PIRSF) classification system. Based on the evolutionary relationships of whole proteins, this classification system allows annotation of both specific biological and generic biochemical functions. The system adopts a network structure for protein classification from superfamily to subfamily levels. Protein family members are homologous (sharing common ancestry) and homeomorphic (sharing full-length sequence similarity with common domain architecture). The PIRSF database consists of two data sets, preliminary clusters and curated families. The curated families include family name, protein membership, parent-child relationship, domain architecture, and optional description and bibliography. PIRSF is accessible from the website at http://pir.georgetown.edu/pirsf/ for report retrieval and sequence classification. The report presents family annotation, membership statistics, cross-references to other databases, graphical display of domain architecture, and links to multiple sequence alignments and phylogenetic trees for curated families. PIRSF can be utilized to analyze phylogenetic profiles, to reveal functional convergence and divergence, and to identify interesting relationships between homeomorphic families, domains and structural classes.

International audience; Electrotactile feedback has been proven effective in improving mid-air interactions in Virtual Reality (VR) scenarios. However, the elicited sensation is often described as unnatural. We explore standard stimulation patterns or effects (FXs) found in the literature and how they can get coupled with common VR interactions. We propose 6 implementations of these patterns and, based on our expectation that some couplings work better than others, we evaluated their coherence in an experiment (N=8).