Patients with Biallelic BRCA1/2 Inactivation respond to Olaparib treatment across Histologic tumor types

Purpose: To assess the efficacy of olaparib, a PARP inhibitor (PARPi) in patients with tumors with BRCA1/2 mutations, regardless of histologic tumor type. Patients and Methods: Patients with treatment-refractory BRCA1/2-mutated cancer were included for treatment with offlabel olaparib 300 mg twice daily until disease progression or unacceptable toxicity. In Drug Rediscovery Protocol (DRUP), patients with treatment-refractory solid malignancies receive offlabel drugs based on tumor molecular profiles while whole-genome sequencing (WGS) is performed on baseline tumor biopsies. The primary endpoint was clinical benefit (CB; defined as objective response or stable disease ≥ 16 weeks according to RECIST 1.1). Per protocol patients were enrolled using a Simon-like two-stage model. Results: Twenty-four evaluable patients with nine different tumor types harboring BRCA1/2 mutations were included, 58% had CB from treatment with olaparib. CB was observed in patients with complete loss of function (LoF) of BRCA1/2, while 73% of patients with biallelic BRCA LoF had CB. In 17 patients with and seven without current labeled indication, 10 and four patients had CB, respectively. Treatment resistance in four patients with biallelic loss might be explained by an additional oncogenic driver which was discovered by WGS, including Wnt pathway activation, FGFR amplification, and CDKN2A loss, in three tumor types. Conclusions: These data indicate that using PARPis is a promising treatment strategy for patients with non-BRCA-associated histologies harboring biallelic BRCA LoF. WGS allows to accurately detect complete LoF of BRCA and homologous repair deficiency (HRD) signature as well as oncogenic drivers that may contribute to resistance, using a single assay

User cognition in product operation

Daily a large number of everyday consumer products are being used. Unfortunately part of this usage is not successful. One of the causes of failure lies in the cognitive aspects of product use, users do not know how to operate the product or try to use it in a way which is not successful. Ideally, the designer of a product should convey information on the use of the product through the design, enabling the user by intuition to operate the product successfully. However, theoretical insights on which this could be based are lacking. The type of insight provided e.g. by psychology into (user's) operating behaviour are such that translation into product design is almost impossible. This study shows the importance of cognitive aspects for everyday use of products and investigates the influence of a number of factors. In a series of six experiments it is investigated how the combination of human cognition (knowledge, experience and expectations) and product features may lead to failing use of unfamiliar models or functions of familiar products like a water tap, can-opener, corkscrew and telephone. Two types of causes are found to be related to the occurrence of operating difficulties with unfamiliar product models, low guessability, the shortage of clues on the use of the product in the design and fixation, the tendency of users to apply familiar operating procedures even when these do not lead to success. On the basis of the results of the first four experiments two relations are formulated regarding the origin of operating difficulties viz. the lack of correspondence between product appearance and product operation and the existing experience of the user. Further testing of these two relations in the last two experiments results in a recommendation concerning the relation between appearance and operation of a designed product. For the supposed relation between type of user experience and the prevention of operating difficulties a less solid confirmation is found.Design, Engineering and Productio

Overview and Categorization of Robots Supporting Independent Living of Elderly People: What Activities Do They Support and How Far Have They Developed

Over the past decades, many robots for the elderly have been developed, supporting different activities of elderly people. A systematic review in four scientific literature databases and a search in article references and European projects was performed in order to create an overview of robots supporting independent living of elderly people. The robots found were categorized based on their development stage, the activity domains they claim to support, and the type of support provided (i.e., physical, non-physical, and/or non-specified). In total, 107 robots for the elderly were identified. Six robots were still in a concept phase, 95 in a development phase, and six of these robots were commercially available. These robots claimed to provide support related to four activity domains: mobility, self-care, interpersonal interaction & relationships, and other activities. Of the many robots developed, only a small percentage is commercially available. Technical ambitions seem to be guiding robot development. To prolong independent living, the step towards physical support is inevitable and needs to be taken. However, it will be a long time before a robot will be capable of supporting multiple activities in a physical manner in the home of an elderly person in order to enhance their independent living

Rehabilitation robotics in robotics for healthcare ; a roadmap study for the European Commission

To gain understanding in the current status of Robotics in healthcare the European Commission issued a roadmap study into this domain. This paper reports on the main characteristics and results of this study. The study covered the wide domain of Healthcare and in this paper the domains relevant for Rehabilitation Robotics are highlighted. The study ultimately resulted in a range of required or foreseen developments foreseen in six areas of Healthcare Robotics regarding societal needs, innovations and technology. These developments were positioned along a timescale running till 2025. This study will guide the policy development of the 7th and 8th framework of the EC. ©2009 IEEE

Effectiveness of Robot Paro in Intramural Psychogeriatric Care: A Multicenter Quasi-Experimental Study

Background: Together with care professionals, specific psychogeriatric care applications were developed for the seal robot Paro. Objectives: This study aims to evaluate the outcomes of the developed Paro interventions, applying the robot in psychogeriatric care. Design: A multicenter quasi-experimental time series ABAB study (n = 91) with within-subject comparison was conducted to assess both the short-term effects of the Paro interventions for therapeutic applications, and the facilitation of daily care activities by care providers. Setting: Small-scale care units (8-10 residents each), spread over 6 different locations, in 3 Dutch care institutions for intramural psychogeriatric care. Participants: A total of 91 patients with dementia, in all stages of dementia. Intervention: Two user-centered intervention types were applied, one for therapeutic purposes and one for the facilitation of daily care activities. Measurements: Effectiveness was measured with a goal attainment scale (IPPA) and a mood scale (Coop/Wonca), by means of a registration form. Results: A total of 106 user-specific interventions were defined for 91 participants; 71 participants completed the study, 14 were men and 57 were women. All interventions combined show a significant effect (P <.001). Conclusion: Paro should be seen as a tool for care staff and not as a replacement of care. Successful implementation of Paro in daily intramural psychogeriatric care practice can increase the quality of care and the quality of life for the elderly

How to use robot interventions in intramural psychogeriatric care: a feasibility study

Background: Social robots, with Paro being an example, offer new opportunities for innovative approaches in dementia care. Objectives: To investigate how interventions, with the socially assistive robot Paro, can be implemented in daily care practice. Design: Paro was used according to individualized interventions, aiming at predefined specific care problems, during a 3-week period. Selected residents were offered Paro once or twice a week. Setting: Small scale care units (8-10 residents each) in three Dutch care institutions for intramural psychogeriatric care. Participants: A total of 23 dementia patients, 22 female and 1 male, participated. Intervention: Three intervention types were applied, one for therapeutic purposes, one for facilitating daily care activities and one to support social visits. Measurements: The experience of care staff, informal caregivers and patients with Paro were registered qualitatively by means of a registration form in which each occasion of Paro use was briefly reported. Additionally, care staff was interviewed using a semi-structured qualitative questionnaire. Results: The 23 residents were involved in 36 individually defined interventions, and in total 71 sessions were carried out. In the majority of cases, care staff and patients considered the Paro interventions to be of added value for the care provided. Conclusion: The use of Paro can be well individualized to the needs of patients, the resulting individual Paro intervention can be well implemented in day to day care, and Paro may have added value when used in a well-directed way