To identify and prioritise the most impactful, unanswered questions for obesity and weight-related research.Prioritisation exercise of research questions using online surveys and an independently facilitated workshop.Online/virtual.We involved members of the public including people living with obesity, researchers, healthcare professionals and policy-makers in all stages of this study.Top 10 research questions to be prioritised in future obesity and weight-related research.Survey 1 produced 941 questions, from 278 respondents. Of these, 49 questions held satisfactory evidence in the scientific literature and 149 were out of scope. The remaining 743 questions were, where necessary, amalgamated and rephrased, into a list of 149 unique and unanswered questions. In the second survey, 405 respondents ranked the questions in order of importance. During the workshop, a subset of 38 survey respondents and stakeholders, agreed a final list of 10 priority research questions through small and large group consultation and consensus. The top 10 priority research questions covered: the role of the obesogenic environment; effective weight loss and maintenance strategies; prevention in children; effective prevention and treatment policies; the role of the food industry; access to and affordability of a healthy diet; sociocultural factors associated with weight; the biology of appetite and food intake; and long-term health modelling for obesity.This systematic and transparent process identified 149 unique and unanswered questions in the field of obesity and weight-related research culminating in a consensus among relevant stakeholders on 10 research priorities. Targeted research funding in these areas of top priority would lead to needed and impactful knowledge generation for the field of obesity and weight regulation and thereby improve population health. This is the first research priority setting specific to the field of obesity and weight-related research.This exercise involved input from a large number of participants from a broad range of relevant stakeholder groups including patients, members of the pubic, researchers, policy-makers and charities.The final list of priorities was reached through consultation and consensus in a workshop guided by independent facilitators to minimise bias towards certain questions or areas.2 (or ≥30 kg/m2 if of white ethnic groups). No country has managed to achieve a sustained decrease in the prevalence of obesity, despite evidence-based clinical and public health guidelines and polices aimed at tackling obesity.Obesity is a major preventable cause of ill health and is affecting an increasing number of children and adults globally.Presently, the research agenda is mainly driven by the interests and concerns of researchers, or research commissioners. A more transparent, systematic and collaborative approach involving multiple stakeholders to identify research priorities could accelerate progress. The James Lind Alliance (JLA) priority setting process brings patients, carers and clinicians together on an equal basis to define uncertainties, consider their importance and thereby set research priorities.We involved two members of the public (BC and PS) with lived experience of overweight in all stages of the project, from conception and design of the study, to its conduct, data collection and analysis. Our wider public involvement (surveys and workshop) incorporated members of the public with and without lived experience of being overweight and patients, defined as people with lived experience of being overweight and experience of receiving clinical treatment for overweight, obesity or an associated condition. Members of the public were involved in all stages of the work alongside and as equal partners with other stakeholders.et al,et al.The priorities for obesity and weight-related research (POWeR) project took place between December 2019 and December 2020. The process was guided by Viergever Gathering questions:The first survey in the process asked respondents to submit up to four questions that they felt should be prioritised in the field of obesity and weight-related research. The survey was administered online using JISC Online Survey and was piloted with our public coauthors and colleagues in the research team, prior to being launched. The survey asked respondents to identify research questions that they felt were the most important unanswered questions on the topic and to say why they felt each question was important. The latter information was used by the team to interpret, contextualise, group and sort questions.https://www.phc.ox.ac.uk/research/participate/power), and actively via email to relevant stakeholders and Facebook adverts targeted to men. We invited our stakeholders to circulate the link, resulting in the distribution of the survey by more than 40 organisations to their members, visitors to their webpages and readers of their newsletters  systematic reviews published within the last 10 years, with little to no uncertainty; (2) proof of evidence in national clinical guidelines . We also accepted primary literature by way of high certainty if there was evidence in randomised controlled trials (RCTs). Such an approach would indicate that the question on currently available pharmacotherapy for obesity, for example, was at least partially answered by current reviews and trials.We noted how many questions fed into each research question.The second online survey was piloted with members of the public and colleagues in the research team. The survey was administered via REDCap, and sent to the 256 survey 1 respondents who had provided us with their email addresses, as well as to the organisations approached to share survey 1 see .The second survey remained open for 30 days between 6 August 2020 and 14 September 2020. Survey 2 asked respondents to prioritise the unanswered questions gleaned from survey 1, which were sent in batches of about 50 questions to lower the response burden. The questions in each batch covered the whole range of submitted research questions. Respondents were asked to rate each question on a scale of 1–10 with 10 representing ‘very important’ and 1 representing ‘not important’. The mean priority score was calculated for the resulting rated questions and ranked  to creatWe invited a subset of survey respondents and other stakeholders including NGO representatives, healthcare professionals, public members including people with lived experience of overweight to take part in a 3-hour online workshop in the winter of 2020 to determine the top 10 questions. This was a real-time, facilitator-led consultation, replacing a full-day in person event that was not possible due to local COVID-19 restrictions. The group was representative of the multidisciplinary stakeholders involved in the project; patients and members of the public, researchers, policy-makers, clinicians and relevant research funders. The workshop was held via a videoconferencing platform (Zoom), and led by external facilitators from Hopkins van Mil, a service that specialises in guiding impartial discussions to elucidate views and opinions of a diverse group of people in a safe, productive space.The 3-hour workshop was divided into three parts with a final plenary session. Throughout the workshop participants were asked to justify their choices, and reveal the values and reasoning behind their prioritisation. Important questions were defined as those that would have the most impact if answered by research. In the first session, each group was asked to debate what they considered to be the four most and least important research questions from the 30 questions. In session 1, the highest and lowest questions were determined.In session 2, facilitators shared a list of questions that were of medium importance, that is, not the highest or lowest priority questions determined in session 1. Facilitators asked participants to categorise these as either: (1) a priority, (2) low priority, (3) not a priority. This was determined by debate, discussion and justification of the participants’ reasoning. The facilitator moved the questions around on the shared slide. The highest ranking questions from session 1 and session 2 were brought together. By the end of the second session each group had a list of top 14 questions ranked in order of importance.The facilitators then met to combine the top 14 questions from all the small groups, this led to one list of 16 questions. In the third session of the workshop, this combined list of 16 questions was shared with the individual groups for debate. Here the groups were asked to determine and rank their final list of 10 research questions. Facilitators guided this final prioritisation stage by asking groups to focus on questions that would have the highest impact if taken forward as a research question. The groups then came together in a final plenary session and the top two questions from each group were shared with the larger group. After an amalgamation of the top two questions from each group and invariable overlap, the third and fourth questions from each group were added to produce a final list of the top 10 questions.https://www.phc.ox.ac.uk/research/participate/powerThis three-stage prioritisation project involved a diverse group of stakeholders in prioritising a list of top 10 unanswered research questions for obesity and weight-related research, which are presented here and at: Demographics of respondents and questions gathered:Survey 1 received 278 responses , yieldinfigure 1Box 1What are the most effective methods for weight maintenance following weight loss? What are the effective components of treatments/programmes incorporating a behavioural element? How many and in what combination are most effective? What is the optimal duration of these programmes?What are the most effective methods for weight loss? What are the effective components of treatments/programmes incorporating a behavioural element? How many and in what combination are most effective? What is the optimal duration of these programmes?What is the most effective and cost-effective mix of population/public health and individual interventions to tackle obesity?Do interventions that target the ‘obesogenic environment’, such as community interventions, urban planning, placement of fast-food outlets or workplace polices, affect population mean weight and do these effects differ by baseline weight status ? Which interventions are most effective at reaching low socioeconomic groups?Do interventions  in preschool, primary school and secondary school reduce children’s risk of unhealthy weight gain and, if so, how do they act? Does the effect of such interventions differ by social and cultural groups?What changes in supermarkets or the wider food industry are effective in promoting healthier diets? Does changing labelling and/or packaging on foods affect purchasing, consumption and body weight?What is the cost and affordability of a healthy balanced diet? How can we make healthier foods more affordable? How can we improve access to healthy diets for social and cultural groups, such as people in poverty, people in inner cities, or young and older people?How do demographic, social and cultural factors  affect weight status, weight gain and regional fat distribution? What are the mechanisms involved? Does the effectiveness of weight loss methods depend on social and cultural background and, if so, can the effects be made more equitable? Are weight loss methods tailored to people’s background more effective for weight loss and weight maintenance than general methods?How accurate are existing models of health consequences of excess weight and the impact of weight loss? Which assumptions are critical in determining the long-term effectiveness and cost effectiveness of weight loss interventions? What do these models predict is the impact of weight loss interventions on health and disease incidence and the cost-effectiveness of such interventions? What is the impact of weight regain on the incidence of disease and cost-effectiveness of weight loss interventions?What are the drivers of food choice, appetite and intake and do variations in these drives explain who develops obesity and who does not? How does the brain control food intake and can we use these mechanism to aid weight loss? What are the brain responses  in response to food during weight loss and following weight regain?Identifying unanswered questions:The 941 questions were grouped by topic. We excluded 49 (5.2%) questions as already answered, and 149, (15.8%) as out of scope . The remSurvey 2 received 405 responses; 61% of respondents reported lived experience with obesity and 74% held an education to degree level or above . A totalWe invited 64 stakeholders, 39 people confirmed their acceptance and one person dropped out on the day. Thirty-eight attendees  were made up of 4 public members, 8 participants from related organisations, 13 researchers, 7 policy makers and 6 healthcare professionals. One person asked for the question on the role of the gut microbiome to be included from the list of 10 extra questions. At the workshop 31 questions were debated in small groups. In the first session the groups sorted questions into highest and lowest priority. In the second session, the top 14 questions were determined by all groups except one that determined their top 10 and another that grouped questions as high medium and low priority. The facilitators combined the lists from all the groups into a list of 16 as many of the top 14 from each group overlapped. In the third session participants ranked the 16 questions into a top 10 list. The top two from all these lists was shared at a final plenary session. Consolidation of the top two questions and the questions ranked third and fourth resulted in 11 unique research questions by the end of the workshop. On analysis of recordings of each group’s discussion, multiple participants noted that two questions in the 11 that were similar in meaning. We, therefore, combined these two questions  post hoc to produce a final list of the top 10 research questions . There wOur priority setting exercise identified the top 10 research questions that stakeholders in the field, and those with an interest overweight and obesity, believe to be the key priorities to advance obesity and weight-related research. In two online surveys and a workshop, we collated nearly 1000 questions, and guided participants in a structured and systematic prioritisation process to reach the final list of 10 . These qThe main strength of this project was the successful collaboration between a diverse range of stakeholder groups, though it was not without its challenges. Our stakeholders included patients, members of the public, clinicians, charities, researchers and policy-makers connected to the field. Identifying the most appropriate group for a condition where a third of the adult population are clinically obese and more than 60% are overweight, while at the same time, considering how to prevent the condition developing which is relevant to the whole population, resulted in the inclusion of both patients and members of the public. Members of the public naturally included some people without lived experience of overweight or obesity, though it seems unlikely that they would not be aware of family members, and friends who are affected, and they may become affected themselves, justifying their inclusion in this prioritisation process. To have found consistency in the questions being posed throughout the entire process by a variety of individuals bringing different experience and expertise to a common area of focus, supports the validity of the resulting top 10 questions. The majority of survey respondents and workshop participants appear to be highly educated. Nonetheless there was evidence of an awareness of the need for interventions to help reduce inequalities and the top 10 priorities include questions on social determinants of health like low-socioeconomic status and cultural factors. We commissioned third-party, impartial facilitators to guide the workshop without input from the research team, so as to not inadvertently sway the prioritisation of questions being considered in each session. Additionally, the number of questions submitted and finally categorised is in line with similar priority setting exercises in health research, using an analogous process set out by the JLA, with a comparable number of stakeholders involved.13 14There are limitations that we identified and strived to address throughout the stages of the process. To begin with survey 1, we deemed that 5.2% of all questions submitted were already answered by empirical evidence. We assessed this through a thorough search of the literature to identify systematic reviews, clinical and public health guidelines and high-quality primary studies in the form of RCTs. Although this necessitated some subjective judgement, we ensured that all decisions were made in duplicate, and discrepancies were resolved by a third researcher. Our confidence in the categorisation of answered versus unanswered questions is strengthened by consensus among stakeholders involved, some of whom were researchers with expertise in the question areas being considered. That 5.2% of the submitted questions were considered answered indicates that research may not being adequately communicated in these areas. This could be addressed by improved or targeted communication.In survey 2, we asked participants to rate questions on a scale of 1–10, but found that participants were disinclined to use the full range. Many questions had means between 6 and 8 meaning that differences in the scoring were subtle. Future work could consider using a condensed scale to perhaps mirror ratings that people are more familiar with (eg, 5-point ratings seen in 5-star reviews or 4-point grading of evidenceAn additional limitation of the workshop was the shift to a virtual vs in-person meeting due to local COVID-19 restrictions, which limited the length of the discussions. On analysis of the recordings from each group’s consultations, it was clear that the virtual setting maintained a clean discussion where moderators were clearly able to garner input from each participant without anyone talking over-another, as may have been the case in an in-person discussion. It was possible to rank the top 10 in the small groups in the workshop, however, it was harder to achieve this with 38 participants in the plenary sessions so we did not seek to order the final 10 priorities. Lastly, obesity is a worldwide problem calling for a global research response, but we only involved UK-based stakeholders. It is likely that the process identified questions that are generalisable outside of the UK, but it is unlikely that this process fully captured priorities that may be relevant to low-income countries or countries with a low prevalence of overweight and obesity.The main implication of this work is for the top 10 POWeR to be considered by funding bodies concerned with advancing the field. Similar priority setting work in other areas of health research have resulted in research calls that reflect priorities identified by stakeholders.We make two recommendations for future priority setting exercises in this area based on what we learnt from the process. The first would be to limit the focus to a prespecified area in the field. The breadth of topic areas produced by the large number of stakeholders engaged was onerous to process, and resulted in high level areas for research. Future exercises may wish to restrict their scope to a certain area of research, such as treatment for people living with obesity, or population-wide prevention strategies to allow more granular questions to emerge. The second would be to incorporate work to boost awareness of the existing research evidence for common questions that were submitted, but deemed to be answered. Questions that were commonly submitted, but already answered and therefore excluded from progressing through the prioritisation process are telling of a discrepancy between published research and knowledge dissemination.We have identified 10 priorities that cover: the role of the obesogenic environment; effective weight loss and maintenance; prevention in children; effective prevention and treatment policies; the role of the food industry; access to and affordability of healthy diets; the sociocultural factors associated with weight; the biology of appetite and food intake and long-term health modelling. Research funders may want to prioritise these questions when considering research proposals, or commissioning programmes of research to answer these key questions.


We developed a brief cognitive behavioural, one-to-one intervention to reduce fatigue impact for patients with inflammatory arthritis. This qualitative process evaluation explored intervention acceptability and potential refinements from the perspective of patients who attended sessions and rheumatology health professionals (RHPs) who delivered the intervention.Interviews were conducted with patients and RHPs from five National Health Service (NHS) sites. Data were analysed using inductive thematic analysis.Twenty-two patients and 11 RHPs participated.Collaborative, non-judgemental consultations: patients valued having space to reflect, where their fatigue was validated. Relevant content, but not ground-breaking: patients appreciated the opportunity to tailor content to individual priorities. Daily diaries were useful to visualize fatigue. Self-awareness: patients reported increased acceptance, sense of control, and confidence to manage fatigue. Degrees of openness to change: sessions prompted patients to engage in behaviour change. For some, complicated lives made it difficult to plan for change.vs clinical practice: RHPs expressed concern about fitting sessions into NHS clinic appointments. It was difficult to offer follow-up sessions within 2 weeks. Collaborating with patients: RHPs reported that patients engaged with the tools and strategies. Some RHPs followed the manual in a linear way, whereas others used it flexibly.Engagement with intervention: RHPs liked training face to face, and sessions were more enjoyable with experience of delivery. Research There is potential for this brief fatigue intervention to benefit patients. Future research will focus on flexibility to fit with local services and creating educational resources to use in a range of contexts. Key messagesPatients valued the collaborative, therapeutic approach of sessions, describing increased feelings of acceptance and control.Rheumatology health professionals liked and enjoyed delivering the sessions, but it was difficult to fit into clinics.Potential refinements include developing content that can be applied in varying contexts and formats.Fatigue is a common, overwhelming and unpredictable symptom in inflammatory arthritis , 2, likeCognitive behavioural therapy is one of the most helpful types of support for inflammatory arthritis-related fatigue. Previous systematic reviews provide evidence that self-management courses that use cognitive behavioural therapy to increase self-efficacy (beliefs in the ability to carry out self-management behaviours) are more effective than interventions delivering information alone .A team from psychology, nursing and occupational therapy designed a brief, low-intensity intervention to address the impact of fatigue on patients with inflammatory arthritis, to be delivered by trained rheumatology health professionals (RHPs), using a manual, over two to four sessions. The first two core sessions were designed to take place face to face and within 2 weeks of each other. Two additional optional sessions could take place face to face or remotely, within the subsequent 4 weeks. It was tested in a feasibility study  .The intervention aims to reduce the impact of fatigue by encouraging patients to link thoughts, feelings and behaviours influencing their fatigue and their responses to it. Requiring buy-in from both patients and RHPs, the intervention uses an ‘ask, don’t tell’ approach, based on techniques of guided discovery and Socratic questioning . The aimThis paper reports on the findings of a qualitative process evaluation nested within FREE-IA, which played a vital role in understanding the acceptability of the intervention from the perspectives of two groups: the patients who attended sessions and trained RHPs who delivered sessions. It also explored how contextual factors might affect implementation, both as a larger national research study and into normal clinical practice. The aims were to understand the acceptability of the intervention and to identify potential refinements to the intervention.Six weeks after the first session, the study coordinator telephoned patients to collect their fatigue score. During this call, patients were asked if they would like to take part in an optional telephone interview to discuss their views and experiences. If they agreed, a consent form and information sheet were posted to the patient, and contact details were forwarded to the process evaluation research fellow (A.B.).The RHPs were recruited via their local principal investigator and were provided with information sheets explaining that they would be invited to take part in an interview. Consenting patients and respective RHPs provided written informed consent by completing the consent form and returning a copy to the study team before interview.Two distinct qualitative data sets were collected from patients who participated in FREE-IA sessions and RHPs who undertook FREE-IA training and delivery.Rheumatology Advances in Practice online). Patients were asked about the content and acceptability of the intervention. The RHPs were asked about training and the potential for integrating the intervention into clinical practice. Interviews were audio-recorded, transcribed verbatim and anonymized.Data were collected via one-to-one interviews by telephone. Interview questions were developed with collaborators and patient partners Just that the fatigue is acknowledged … having a medical professional sit in front of you and say, ‘This is a thing … we understand it’s a thing, we can’t explain why it’s a thing and we can’t give you a tablet to fix it, but we understand it is a thing’.(D466)Patients reported developing positive therapeutic relationships with experienced and knowledgeable RHPs. They felt it was beneficial to have their fatigue validated and to have time and space to reflect on its impact.Talking through my specific challenges with a bit of space, and a specialist to give me fresh ideas and not judge me … that one-to-one support and the time to talk about it has been very, very welcome … very, very, helpful.(D468)They found the ask don’t tell approach helpful and expressed their preference for a responsive, flexible approach to sessions, rather than a rigid, protocolized approach.It reinforced really what I should do, and what I needed to think about, and that was helpful. … I mean I knew about trying to get proper sleep and relaxation. Trying to pace oneself, those kinds of things. It’s a case of understanding this, you don’t always remember to do it like that.(C343)Patients appreciated the range of topics covered and valued the ability of RHPs to tailor content to individual priorities. Some had explored the topics covered previously; however, using visual illustration, for example, to communicate complex issues was very useful and prompted new ways of looking at the issue.You don’t make any real connections, but when you see it … that was a very good visual clue, and I didn’t think that was going to be useful, but actually, I found probably the most useful. It’s such a visual representation of what you are doing or where you are slacking or crashing or whatever it may be.(D465)That was the biggest wake-up call for me … looking at the activity diary. Until you look at it—you could see that I didn’t have any pattern or any sort of resemblance to any normality at all. Everything was just chaos.(B221)Being able to visualize the impact of lifestyle patterns on their fatigue using the daily activity diaries was helpful.It just feels like I’ve got more control over fatigue … it’s given me permission and a licence to give myself that care, which I don’t think I was allowing myself before.(D468)Some days … take you into nothing but red activity, and today is heading in that direction. I will be ill if I allow that to happen, therefore it’s in my control. I can either do something about it and not feel so bad tomorrow or ignore it and not be able to get up tomorrow.(B229)Sessions increased patients’ awareness of lifestyle factors and patterns influencing their fatigue, which increased their sense of control and confidence to manage fatigue.It’s not the be all and the end all now. I accept it is part of the condition, I accept that it might be there more prominent some days than others or some weeks than others. And there’s no point worrying about it.(A103)Patients also highlighted how the sessions helped them to accept their fatigue, with this reflective process giving them ‘permission to relax’.It started me … paying a bit more attention to things like sleep and diet and lifestyle, but actually specifically thinking about how those could affect the fatigue. … I’m sure the sessions helped with that.(C344)Sessions prompted some patients to engage in positive behavioural change, such as adapting sleep patterns, pacing, planning and setting goals.It’s very easy to get into a rut and just do each day as it comes, and don’t even think about going forward or anything else. … Having things to aim for … I have already booked a few things and doing things in the future.(D465)For others, the sessions ‘sowed the seeds’ and led to planning for future lifestyle changes.I think my condition is governing my fatigue and I don’t think there’s anything that … I think it is what it is, and I think for me the big thing is being more aware of it.(D461)However, some patients felt that any change in lifestyle would not affect their symptoms of fatigue.For some participants, the broader effects of complex lifestyle situations meant it was difficult to consider or plan for change. Co-morbidities, work and family commitments and lack of finances meant that engaging with positive lifestyle changes was impossible.Eight RHPs participated in interviews, and three RHPs provided data via email. Three themes capture their views and experiences.You get much more engagement when you’re face to face and you’ve got the different dynamics going on in the group … we would discuss the course together and different opinions … I thought it was really good.(ATTM1)The RHPs valued the face-to-face training delivered by the FREE-IA team and learning with peers, describing sessions as providing an opportunity to share ideas for learning.We all came out all guns blazing (following training), and then … it was a long time before we were able to get on the ground and see people. You kept re-reading the book, but I think it would have been probably better from my idea to have a refresher.(ETTM1)Some RHPs felt they would have benefitted from refresher training, when starting the sessions was delayed for local logistical reasons.As I’ve been doing the sessions, the more confident I’ve got, part of it is knowing the people, but also knowing the material as well. I’ve really enjoyed it, because you can see how much a patient is getting out of it.(CTTM1)Yes, ‘ask, don’t tell’—very, very difficult. Because, I mean, by nurses … by definition, we advise our patients on theoretically what we think is best for them … it was quite hard to let go. That was very new. … I think familiarity … the more I did it, the easier it became.(ETTM1)For RHPs with extensive experience of providing fatigue support, the low level of treatment intensity and manualized approach limited the usefulness of the intervention. This led to a lower level of engagement and satisfaction compared with RHPs who had fewer resources to use with patients. Conversely, those with less experience of providing fatigue support before the study reported gaining confidence as they delivered more sessions.If we were to focus on fatigue alone, no it wouldn’t (work) … if it’s like a five-minute discussion on fatigue and how to manage it, then that’s fine … but anything longer than that … we wouldn’t fit it in.(BTTM1)Sessions were often carried out outside of usual clinics, or at the end of a clinic in order that more time could be allocated if needed. The RHPs expressed concern about fitting sessions into clinic appointments, because a number of sessions lasted longer than the 20–30 min suggested length. Sessions ranged from 10 to 120 min, with an average (median) of 40 min.That was quite difficult because of the waiting list I have. Getting them in the first time was all right, but getting them in for the second appointment within a fortnight was quite difficult.(ETTM2)It was a challenge to offer patients a follow-up session within the desired 2-week time frame, because of long waiting times and a high demand for available clinic appointments.I have already taken advice from the manual and repeated it to patients in clinic. Snippets of useful information is a quick and easy way of helping patients when I am more pressed for time in a ‘normal’ clinic setting.(DTTM1)Some RHPs described integrating the intervention approach and materials into their routine interactions with patients.Obviously, the activity diaries … I think they look at it, not realizing the actual impact it has, once they’ve done it … they don’t realize until they do it.(CTTM1)The RHPs reported that patients were willing to try the tools and strategies during the sessions. Some RHPs followed the manual in a linear way, whereas others adapted content and used it more flexibly.Most of the ones who contributed to the study are proactive and want to change, and they are willing to make changes. And then you have got other patients … who think that we can fix them by giving them a tablet, and we can’t. And they put up obstacles about everything you say … but I understand it’s hard…(BTTM1)The RHPs also reflected on those patients who did not engage, expressing that some might require a higher-intensity approach and level of support.A key finding within this study was the value of the collaborative, ‘ask, don’t tell’ approach adopted in sessions. Having space and time to discuss the impact of fatigue and having it validated by a health-care professional was empowering. Patients and RHPs described how this approach enabled them to develop positive therapeutic relationships. Some RHPs found using the approach challenging, and this is where more training or experience of the intervention could have strengthened skills and confidence levels of the RHPs.These findings align with previous literature that highlights the importance of shared decision-making and collaborative working relationships . They stPatients and RHPs highlighted the value of particular tools and approaches, such as using the daily diaries to visualize lifestyle patterns. It is important to recognize elements of the intervention that might be incorporated more easily than others. Adapting the daily diary tool for use in everyday clinics could be explored in future research.The RHPs became more confident about the (often new to them) interventional approach and content as they delivered more sessions. These findings support earlier fatigue studies  and litePatients valued working with a health professional who was familiar to them. The RHPs were able to deliver the sessions, but reported barriers to implementing the intervention into normal practice (in its current format) owing to short clinic appointment slots and the inability to carry out the second session within 2 weeks. Some RHPs had adopted certain tools and topics, using them in everyday clinic appointments. This is an important finding and highlights the possibility of adapting intervention content to make it more acceptable and exploring how it could be incorporated better into a clinical setting.For some participants, the broader determinants of health impacting levels of fatigue were complex and multidimensional, and factors such as disease activity meant that it simply was not the right time for change. These findings highlight that a low-intensity intervention will not be adequate for all patients experiencing symptoms of fatigue, but recognizing that it has a place within a ‘stepped approach to care’ , being bThis study was able to uncover the experiences and attitudes about the sessions from the perspectives of both the patient and the RHP. It demonstrates sensitivity to context and the wider determinants affecting fatigue, in addition to highlighting the importance of the collaborative approach of the sessions. The methods adopted were able to unpick the workings and nature of the sessions, including issues affecting approach, content and delivery.The sample was recruited from across all five NHS sites and included participants who had attended between one and four sessions to gain insight into their reasons for opting to take part in more or less of the intervention. Recruitment occurred throughout the course of the study, enabling the sample to include patients who had sessions with RHPs who had differing levels of experience of delivery. Two patient research partners were involved in the design of the study; this included feedback on patient information sheets and interview questions.The sample size, although relatively small at 22, was close to half of the total number of 46 patients who attended sessions; however, ethnic minority communities were underrepresented in the sample. We also collected no data on the health literacy levels of the patients, which are known to affect self-management strategies in rheumatology . It is aA sensible next step is to explore options for alternative modes of intervention delivery and, importantly, how the essence of the sessions, including the approach and tools, might best be translated. The move to online consultations since the coronavirus disease 2019 (COVID-19) pandemic in 2020 opens up the opportunity for more patients to engage with RHPs, but also presents challenges in terms of accessing intervention resources and working collaboratively. Digitalized content could make it easier for RHPs to provide guidance and copies of the diaries before the first session, meaning that lifestyle patterns can be explored together in the initial session.Arguably, online working shows potential for how it might be possible to integrate such sessions into clinical appointments. It would be of value to explore this further with RHPs post-COVID-19, in addition to observing what the ‘new normal’ looks like for different rheumatology clinics nationally.Given the findings of the importance and value of the collaborative nature of the sessions, future research should explore whether and how this approach translates into the digital consultation, and if it is affected in any way, from the perspectives of both the patient and the RHP. Future research will focus on adopting new ways of integrating sessions and content into potentially digital consultations and developing content that can be used in a range of contexts and formats.This study reports on the acceptability of a brief, cognitive behavioural, one-to-one intervention to reduce fatigue impact within the NHS. The study presents novel key issues regarding the usefulness for this new intervention and demonstrates the potential for this intervention to benefit patients. Collaborative, positive therapeutic relationships were able to be established between patients and RHPs within a short period of time, and patients described feeling empowered, more in control and confident to address lifestyle patterns and consider positive behavioural change to improve self-management of their fatigue.rkac064_Supplementary_DataClick here for additional data file.


Both these two parameters can be used to sense different breathing conditions, such as normal breathing and deep breathing, and breathing with different rates such as normal breathing, slow breathing, apnea, and fast breathing. Experimental results also indicate that the proposed humidity sensor has potential applications in predicting the fitness of individual and in the medical field for detecting body fluids loss and daily water intake warning. The respiratory rates measured by our proposed PI-FBAR humidity sensor operating in frequency mode and S11 mode have Pearson correlation of up to 0.975 and 0.982 with that measured by the clinical monitor, respectively. Bland–Altman method analysis results further revealed that both S11 and frequency response are in good agreement with clinical monitor. The proposed sensor combines the advantages of non-invasiveness, high sensitivity and high stability, and it has great potential in human health monitoring.Respiration monitoring is vital for human health assessment. Humidity sensing is a promising way to establish a relationship between human respiration and electrical signal. This paper presents a polyimide-based film bulk acoustic resonator (PI-FBAR) humidity sensor operating in resonant frequency and reflection coefficient S Respiration is one of the vital signs of human beings because it can help assess an individual’s health condition and screen for early diseases based on information from respiratory rate and depth. Abrupt changes in respiration rate and depth often indicate the occurrence of illnesses, such as heart disease, bronchitis, asthma , pneumonRecently, humidity sensors with merits such as fast response, high accuracy, and reliability have been emerged as great candidates for the application in respiration monitoring, which is achieved by measuring changes in humidity during exhalation and inhalation. The drop in local relative humidity (RH) during inhalation, due to the air flow taking away the water vapor, and a subsequent rise in local relative humidity during exhalation due to the increased outflow of water vapor in the breath, happen during respiration, irrespective of the relative humidity of the environment. Therefore, relative humidity sensor-based respiration monitoring is less affected by the environmental conditions as compared to the mechanical sensors, conventional air flow meters and thermal sensors. Generally, there are various kinds of humidity sensors, such as optical fibers ,8,9, capA lot of effort has been invested to realize high-performance FBAR humidity sensors. Hygroscopic materials such as polymers , graphen11 [11 response of the PI-FBAR humidity sensor [11 has not been systematically studied. In addition, as far as we know, there is no report on human respiration monitoring based on FBAR humidity sensor, especially the new detection method of S11 parameter response for respiration monitoring.To solve the above-mentioned problems of the FBAR humidity sensor based on mass adsorption, our research group previously proposed a FBAR humidity sensor based on polyimide (PI) Young’s modulus modulation  rather t11 , we furty sensor . Results11 dual-parameter sensing was analyzed, designed, fabricated, and tested. The application of PI-based high-performance FBAR humidity sensor in real-time respiratory monitoring was performed. The responses of both the two parameters of resonant frequency and S11 to respiratory monitoring were experimented and compared. Both parameters were used to sense and monitor different rates of breathing, such as normal breathing, apnea, slow breathing, and fast breathing, as well as to sense the difference between oral and nasal breathing. Besides, a comparative analysis of the respiratory characteristic curves before and after exercise was carried out to predict the fitness of individual, especially for athletes. The respiration signals before and after water drinking were also well recorded and systematically analyzed for daily water intake warning. In order to prove the accuracy of the proposed PI-FBAR humidity sensor in human respiratory monitoring, respiratory rate test results of our prepared sensor operating in resonant frequency and S11 dual-parameter were compared with that measured by a clinical monitor.In this work, a PI-based FBAR humidity sensor operating in resonant frequency and reflection coefficient S11 is not clear, and it is tentatively presumed to be caused by the change in acoustic loss caused by water molecules. To explore the humidity sensing mechanism of S11 more systematically, Mason equivalent transmission line model [Though, it has been verified in our previous work  that thene model  is used Parameters in the above Mason model are defined as follows:The acoustic impedance As can be seen in Equation (2), the properties of PI-FBAR are related to the elasticity coefficient Other parameters in Mason model are as follows: Given the thickness and material parameters of each layer of PI-FBAR, as shown in 11 value of the resonator. In order to explore the modulation effect of attenuation factor 11, we simulated and analyzed the relationship between S11 and the change in 11 increases from −32 dB to −30 dB. Although the related expression cannot be given due to the complex relationship between the attenuation factor and humidity, the simulation results show that the increased PI viscoelasticity caused by the increase in humidity will lead to an increase in the value of S11.As we all know, PI is a porous polymer material, whose viscoelasticity will change with the change in humidity . As the 2 sacrifice and insulation layer, deposition and patterning of Pt bottom electrode, magnetron sputtering and patterning of ZnO piezoelectric film, deposition and patterning of Pt top electrode, spin coating and patterning PI layer, and etching SiO2 and Si from the back side. After the proposed sensor chip was prepared, the chip was fixed to the PCB board so that the sensor chip and the PCB board can be electrically interconnected by the gold wire ball welding technology, and then connected to the vector network analyzer through the SMA interface for subsequent testing.The designed PI-FBAR sensor chip was fabricated with the MEMS process described in our previous works ,25, inclThe preparation of PI film is crucial because it acts as both the supporting structure and the humidity sensitive structure. The polyamide acid solution used for the preparation of PI film is ZKPI-305IIE, purchased from Beijing POME Technology Co., LTD . The specific preparation process of PI is shown in 11 of the resonator. Specifically, as the ambient humidity increases, the PI absorbs moisture, which increases the resonant frequency and the S11 value. As the measured ambient humidity decreases, PI desorbs moisture, which reduces the resonant frequency and the S11 value.As discussed in our previous works ,25, due 2CO3 and KI. The proposed humidity sensor was inserted into a closed glass bottle and placed above the level of a saturated salt solution. A vector network analyzer  combined with the LabVIEW program was used to measure and record the real-time change in the resonant frequency and S11.The sensing performance test system of the PI-FBAR humidity sensor is shown in 11 responses of the respiratory rate with that measured by a clinical monitor , which obtains the breathing signal from the impedance change caused by human breathing.The diagram of the real-time human breathing monitoring system is shown in 11 from those reported in previous work may be due to the slight difference in the thickness of ZnO during magnetron sputtering and the difference in the surface properties of PI film.11 response, which may be caused by the fact that the frequency response requires a longer time to absorb and desorb humidity, and the frequency response is less stable than the S11 response. The baseline drift would be improved if the latency of the test in The prepared PI-FBAR humidity sensor was placed into different saturated salt solutions in equilibrium state with different relative humidity (RH) to test its humidity response characteristics. It should be pointed out that the sealed bottle with desiccant is regarded as 0%RH. Keep the humidity sensor in an airtight container with desiccant for 120 s, of which the RH is regarded as 0%, then quickly place it in a saturated salt solution with certain RH for 40 s, then place it in an airtight container with desiccant for 120 s, repeat this operation, until these different humidity environments of 11%, 33%, 50%, 75%, and 98% are repeated. Specifically, due to the large hysteresis from a high humidity environment of 98% to a dry environment of 0%, this process lasted for 3 min to make the sensor as pristine as possible. In order to test the continuous response stability of the humidity sensor, we conducted three rounds of experiments. The humidity response results are shown in 11, calculated by Equation (3), were shown in The humidity response sensitivity (S) of resonant frequency and S11 response sensitivity showed higher linear sensitivity at low humidity and lower linear sensitivity at high humidity. The reduced sensitivity in high humidity environment is mainly caused by the PI mass loading effect in high humidity environment, which reduced the frequency of the resonator, thereby offsetting the value of the frequency increase caused by the increase in PI’s Young’s modulus. For the lower relative humidity from 0% to 33%, the sensitivity of the resonant frequency and the S11 response are 56 ppm/RH and 964 ppm/RH, respectively, and for the higher relative humidity from 33% to 98%, the sensitivity of the resonance frequency and the S11 response are 15 ppm/RH and 570 ppm/RH. Although the sensitivities of both parameters are reduced in higher relative humidity environments, they are still sufficient for subsequent human respiration monitoring applications. Results showed that the sensitivities of S11 in both high and low humidity environments are several tens of times higher than those of resonant frequency.Both the resonant frequency and the S11 response have good repeatability, and the stability of S11 is even better than that of the resonant frequency response.Besides, in order to analyze the stability of the sensor more intuitively, we compared the response results of three rounds of experiments, as shown in 11 responses for 6 h in different humid environments . As shown in 11 response, respectively, these two responses showed that the proposed sensor possesses high stability with small errors.Apart from that, the sensor’s stability was tested by measuring the resonant frequency and S11 with periodic changes in humidity from 0 to 98% were shown in 11 response, the time of 63% and 90% complete adsorption response are 6 s and 15 s, respectively, and those of desorption response are 7 s and 19 s, respectively. For the resonant frequency response, the time of 63% and 90% complete adsorption response are 5 s and 12 s, respectively, and those of desorption response are 9 s and 26 s, respectively. These results showed that the resonant frequency response is faster than that of S11 in the process of moisture absorption, while the response of S11 is faster than that of the resonant frequency in the process of desorption. The humidity response performance of both parameters is sufficient for most humidity detection applications. In addition, study [The real-time responses of the resonant frequency and Sn, study  has showComparisons of the performance of our designed sensor in this work with some other piezoelectric acoustic resonant humidity sensors in previous literature are listed in 11 curves, shown in 11 during expiratory periods, while there was a decrease during the inspiratory periods. This can be attributed to the fact that a large amount of water vapor is brought in when exhaling, causing the humidity to rise, while most of the water vapor is taken away due to the air flow when inhaling, making the humidity decrease, which is consistent with the sensor’s frequency and S11 response of humidity as described above. The results shown in 11 parameters caused by deep breathing are greater than that of normal breathing, which may be attributed to the significantly large volume of air movement during the deep breathing process. Additionally, deep breathing is usually accompanied by a decrease in respiratory rate (RR). These significant differences between normal and deep breathing suggested the applicability of the fabricated PI-FBAR humidity sensor for identification and diagnosis of several health conditions such as asthma, tachypnoea, etc.Monitoring of different breathing conditions was performed on a healthy adult volunteer to study the feasibility of the PI-FBAR humidity sensor performance see . During 11 variation during oral breathing are greater than that of nasal breathing. The frequency shift of nearly 0.4 MHz and a change in S11 value nearly 0.2 dB were observed during the nasal breathing, whereas a frequency shift of nearly 0.6 MHz and a change in S11 value nearly 0.3 dB were observed during the oral breathing. The increase in the changes in frequency and S11 in case of oral breath is attributed to the large intake of air volume and subsequent increase in number of molecules interacting with the sensor as compared to that of the nasal breath. Furthermore, the presence of nasal mucosa creates filtered air which may also affect the overall humidity during the nasal breathing mode.Performance of the fabricated sensor under different breathing modes, such as nasal breathing and oral breathing, was also analyzed. As shown in 11 and frequency of the humidity sensor for nasal breathing with different respiration rates are demonstrated in The fabricated sensor was thereafter used for continuous inspection on respiration rate (RR). For normal adults, the normal breathing rate is 12–20 per minute, and breathing rates outside the normal range may indicate health problems. The response curves of S11 can efficiently distinguish between varying breathing rates, indicating their potential for real time health monitoring.The respiration rates for slow, normal, and fast breath modes observed in 11 or frequency change in every respiration state. In case of nasal breathing before vigorous exercise, as shown in 11 response are 16 per minute and nearly 0.15 dB, and those calculated from resonant frequency response are 16 per minute and nearly 0.32 MHz. However, in the case of nasal breathing after vigorous exercise, as shown in 11 response change to be 36 per minute and nearly 0.11 dB, and those calculated from resonant frequency response are 36 per minute and nearly 0.22 MHz.The respiration rate (RR) and depth of respiration (DR) before and after climbing six floors were also monitored and breathing index (BI) was calculated to estimate the fitness level of five individuals. As can be observed from The empirical metric, Breathing Index (BI), is defined as the ratio of respiration rate to the depth of respiration under light and vigorous exercises . In our 11 response were calculated to be approximately 1.55 (>1) and 1.65 (>1), respectively. Results (BI > 1) revealed that subject 2 exchanged a larger volume of air during climbing six floors than he did during rest state. The calculated BIs of the five subjects were shown in 11 can be used to efficiently predict the fitness of individual, especially for athletes.By using Equation (4), the BI of subject 2 at frequency response and S11 and resonant frequency increased after water intake, and then showed a tendency to decrease over time, indicating the process of water loss. Results proved that our sensors have the potential application in the medical field for detecting the loss of body fluids and daily water intake warning.As one of the indicators of personal health, daily water intake can also affect respiratory humidity. Respiration signals of the proposed PI-FBAR sensor were also recorded before and after water intake, and the dynamic response curves of nasal breathing were plotted in 11 parameters to different breathing modes and breathing states is better than that of resonant frequency, which is manifested in the smaller glitch of the waveform and more balanced amplitude, indicating that the S11 parameter is more suitable for respiration monitoring.In summary, our proposed humidity sensor can not only record the user’s respiration rate and respiration manner, but also predict the fitness and monitor the dehydration of individual, which is useful for patients’ clinical nursing. More notably, from the monitored signal curves, the response of S11 responses with that measured by the clinical monitor. The experimental comparison results are shown in 11 and resonant frequency response results with that of the clinical monitor, in the range of different respiration rates ranging from a few to three dozen, were 0.982 and 0.975, respectively. The highly correlated results with clinical monitor demonstrated the reliability of our fabricated sensor for respiratory monitoring.In order to further prove the accuracy of the proposed PI-FBAR humidity sensor in human respiratory monitoring, we compared the respiratory rate test results of the sensor’s resonant frequency and S11 and resonant frequency response results with that of the clinical monitor were also analysed by Bland–Altman method [11 and frequency response with that measured by clinical monitor were  and , respectively. The results showed that most of the differences fall within the 95% confidence interval. After analysing the original breathing signal, it can be seen that very few points with larger differences are due to the sudden change in the breathing rate. Different breathing rate extraction algorithms lead to inconsistency in the calculation results of the breathing rate. Anyway, results showed that both S11 and frequency response are in good agreement with clinical monitor, and the results measured by S11 had better consistency.In addition, the consistency of Sn method . Its bas11 dual-parameter was proposed and fabricated for real-time human respiration monitoring. The proposed PI-FBAR sensor operating in resonant frequency was governed by the modulation of the humidity on the Young’s modulus of PI, which is different from the conventional FBAR governed by mass loading effect, whereas the proposed PI-FBAR sensor operating in S11 was based on the modulation of the humidity on attenuation factor of PI layer. Humidity response test results showed that both resonant frequency and S11 dual parameters exhibit high sensitivity and stability, and particularly, the sensitivity of the S11 mode was dozens of times higher than that of the frequency. The prepared dual-parameter PI-FBAR, especially that operating in S11 mode, was proposed for the first time for human respiration monitoring. Results showed that both the frequency shift and reflection coefficient S11 variation can be used to sense different breathing conditions, such as normal breathing and deep breathing, normal breathing, slow breathing, apnea, and fast breathing by detecting respiration rate and depth of respiration. They can also be used for detection in different breathing modes, such as nasal breathing and mouth breathing. Experimental results also indicated that the proposed humidity sensor had potential applications in predicting the fitness of individual and in the medical field for detecting body fluids loss and daily water intake warning. The respiratory rate measured by our proposed PI-FBAR humidity sensor operating in frequency mode and S11 mode has a Pearson correlation of up to 0.975 and 0.982 with the respiratory rate measured by the clinical monitor, respectively. Bland–Altman method analysis results further showed that both S11 and frequency response are in good agreement with clinical monitor, and the results measured by S11 had better consistency. In summary, our proposed sensor combines the advantages of non-invasiveness, high sensitivity and high stability, and holds tremendous potential in human health monitoring.In this work, a polyimide-based film bulk acoustic resonator (PI-FBAR) humidity sensor operating in resonant frequency and reflection coefficient S


It was found that the dependence of the current in the graphene film on the frequency of the surface acoustic wave (SAW) excitation repeats the amplitude-frequency response of the SAW delay time line. It is shown that increasing the SAW amplitude leads to an increase in the current in the graphene film, and the current in the graphene film depends linearly on the amplitude of the high-frequency input signal supplied to the interdigital transducer . It is demonstrated that at a positive bias potential on the graphene film, the SAW propagation allows to change the direction of the current in the graphene film by changing the amplitude of the SAW. It is also shown that in the frequency range of the amplitude-frequency response of the SAW delay time line, the current in the graphene film can vary from positive to negative values depending on the frequency. The capability to control the SAW excitation frequency or the SAW amplitude makes it possible to control the value and direction of the current in the graphene film. The SAW propagation lets to collect and transport the photo-stimulated charges in the graphene film on the crystal surface.The process of acoustically stimulated charge transport in the graphene film on the surface of the  Modern acoustoelectronics is based on the use of surface and bulk acoustic waves for the transmission and processing of information in a real time mode . Also, aRecently, the development of gas sensor acoustoelectronic devices is associated with the use of 1D (ZnO and AlN nanorods) and 2D crystals (graphene and graphene oxide) ,8,9,10. An interesting proposal is to use the surface acoustic waves in solar energy for acoustically stimulated transport of charge carriers generated in semiconductor structures under the influence of light ,12,13,143 ferroelectric crystal depending on the SAW amplitude and the bias potential on the graphene film. The process of charge transport in a graphene film under the conditions of generation of electron-hole pairs under the action of optical radiation is also studied.The purpose of these investigations is to study the process of the SAW propagation in the graphene film on the surface of a LiNbO3 crystal was used to study the process of the SAW propagation in the graphene film. This crystal cut has large values of piezoelectric moduli and a large value of the electromechanical coupling coefficient. The process of SAW propagation in the 3 crystal is characterized by the autocollimation of the acoustic beam. The velocity of SAW propagation in the 3 crystal is 3 crystal is 3. The substrate surface has been polished. The substrate roughness does not exceed 3 Å at the damaged layer thickness of 24 Å.The 3 crystal. The IDTs (input and output) were fabricated by photolithography and consisted of 25 pairs of Al electrodes. The period of the IDT electrodes was 15 μm, which corresponds to the SAW wavelength Λ = 30 μm. The aperture of the IDT was W = 50 × Λ = 1500 µm.A SAW delay time line consisting of two identical interdigital transducers (IDTs) was fabricated on the surface of the 3 crystal. In the left part of the spectrum, strong peaks of the LiNbO3 crystal are visible. The inset shows a zoomed-in part of the spectrum, in which the peaks of graphene  are visible. The spectrum demonstrates features characteristic of single-layer graphene, namely, a symmetric 2D peak with a full width at half-maximum FWHM = 28 cm−1 and intensity ratio I2D/IG = 2.1 [3 substrate are marked by asterisks.IG = 2.1 ,27. In tTo study the acoustically stimulated charge transport on the graphene surface, four gold electrodes were fabricated . The disUsually, to study the operation of acoustoelectronic devices (in our case the SAW delay time line), the amplitude-frequency characteristics are measured, which compare the electrical signals at the input and output interdigital transducers. To study the process of the SAW propagation on the surface of a piezoelectric substrate with graphene, a scanning electron microscopy method was used to visualize the SAW in real time ,29,30. TTo study the process of charge transport in the graphene film by the surface acoustic wave, the scheme shown in 3 crystal allows to change the direction of charge transport in the graphene film. In endences  and on tendences  are deteU=−80 mV a in the   leads to an increase in the current in the graphene film. The dependence of the current in the graphene film depends linearly on the amplitude of the input signal on the IDT in dB.The process of acoustically stimulated charge transport in the graphene film on the surface of the At a positive bias potential 3 crystal, has been demonstrated. The SAW propagation allows the collecting of the photo-stimulated charges and transferring them in the graphene film on the substrate surface. This method of charge collection and transfer will significantly improve the efficiency of solar cells in the future.The possibility of the transport of the photo-stimulated charges by the surface acoustic wave, i.e., the charges generated by the optical radiation in the ferroelectric substrate of the


MXene/graphene composites possess high potential in future biomedical applications.The hybridization and surface functionalization of MXene-graphene composites should be further explored to improve the biocompatibility, high stability, and multifunctionality.The synthesis methods, performances, potential toxicologies, as well as future perspectives of MXene/graphene composites are discussed. MXenes, transition metal carbides and nitrides with graphene-like structures, have received considerable attention since their first discovery. On the other hand, Graphene has been extensively used in biomedical and medicinal applications. MXene and graphene, both as promising candidates of two-dimensional materials, have shown to possess high potential in future biomedical applications due to their unique physicochemical properties such as superior electrical conductivity, high biocompatibility, large surface area, optical and magnetic features, and extraordinary thermal and mechanical properties. These special structural, functional, and biological characteristics suggest that the hybrid/composite structure of MXene and graphene would be able to meet many unmet needs in different fields; particularly in medicine and biomedical engineering, where high-performance mechanical, electrical, thermal, magnetic, and optical requirements are necessary. However, the hybridization and surface functionalization should be further explored to obtain biocompatible composites/platforms with unique physicochemical properties, high stability, and multifunctionality. In addition, toxicological and long-term biosafety assessments and clinical translation evaluations should be given high priority in research. Although very limited studies have revealed the excellent potentials of MXene/graphene in biomedicine, the next steps should be toward the extensive research and detailed analysis in optimizing the properties and improving their functionality with a clinical and industrial outlook. Herein, different synthesis/fabrication methods and performances of MXene/graphene composites are discussed for potential biomedical applications. The potential toxicological effects of these composites on human cells and tissues are also covered, and future perspectives toward more successful translational applications are presented. The current state-of-the-art biotechnological advances in the use of MXene-Graphene composites, as well as their developmental challenges and future prospects are also deliberated. Due to the superior properties and multifunctionality of MXene-graphene composites, these hybrid structures can open up considerable new horizons in future of healthcare and medicine. For iactivity . In addi devices .Fig. 1MX3C2Tx)-graphene hybrid aerogels with aligned cellular microstructures were prepared through hydrothermal assembly followed by directional-freezing and freeze-drying processes [–1) exhibited superb electrical conductivity (695.9 S m–1) and EMI-shielding effectiveness (more than 50 dB in the X-band at a low MXene content of 0.74 vol.%) [3C2Tx)-graphene composite aerogel electrodes with high conductivity and large specific surface area were constructed utilizing self-healing polyurethane (outer shell) [MXene-graphene hybrids with high conductivity, thermal stability, and excellent EMI have found their applications in designing novel supercapacitors and multifunctional sensors , 23. 3D rocesses . These p4 vol.%) . Additior shell) . Likewisr shell) . Since, via the selective removal of “A” layer from their MAX or non-MAX phase parents by acid etching, where A is generally group 13 or group 14 elements in the periodic table [via heating [MXenes have been typically prepared ic table , 28. Addic table , chemicaic table , molten ic table , hydrothic table , and eleic table . Chemicaic table . Notablyic table . On the  heating .3C2Tx)/reduced graphene oxide structures were prepared at low temperature (65 °C) followed by a freeze-drying process. In the hydrothermal reaction, ascorbic acid was utilized to prevent MXene structures from being oxidized /reduced graphene oxide aerogels were synthesized via a hydrothermal technique under a temperature of 95 °C. The designed electrodes from these hybrid aerogels exhibited high electrochemical activities, including significant capacity (~1270 mAh g−1 at 0.1C), enhanced cycling life (~500 cycles), and low capacity decay rate (~0.07% per cycle), with excellent areal capacity (5.27 mAh cm−2). Such composites with unique properties should be further explored for constructing intelligent devices with biomedical potentials [Various physical and chemical approaches have been reported for the synthesis of MXene/graphene composites, including mechanical mixing, self-assembly method, hydrothermal technique, heat treatment, and reagent reduction treatment. Among them, hydrothermal techniques have been widely applied to prepare composites. For instance, MXene Ti3CTx/reducetentials .Fig. 2Th−1) [Several methods have been reported for synthesizing MXenes and graphene based on green chemistry principles to avoid the utilization of toxic/harmful agents and laborious processes. However, greener methods for synthesis and functionalization are still in the infancy stages, and more elaborative studies should be planned to find low-cost, simple, up-scalable, and environmentally benign techniques for the synthesis of these structures. In one study, MXene nanosheets were synthesized using an electrochemical method without using dangerous acid/alkali etchants; although the prepared MXenes exhibited high stability and battery performance, it should be further explored for a variety of applications . Greener−1) .Fig. 3Th2N) quantum dot-based systems with high stability and targeting/selectivity properties were introduced with cancer photoacoustic imaging and photothermal therapy potentials [3C2Tx) structures with cellular uptake features exhibited high transferring potentials from vascular endothelial cells with localization, stability, and auto-fluorescence advantages at different emission-excitation wavelengths allowing post-transport examination and tracking [e.g., face masks) [3C2) could be applied for recognition of human papillomavirus (HPV) with high selectivity and fluorescence quenching ability to dye-labeled single-stranded DNA (ssDNA) as well as significant affinity for ssDNA and double-stranded DNA (dsDNA) [MXenes and MXene-based (nano)structures possess abundant functional groups on their surfaces, offering modification/functionalization opportunities with flexibility. In addition to their high stability and hydrophilicity, they also contain complete metal atomic layers and tunable composition which make them attractive candidates for clinical and biomedical purposes . For instentials . Furthertracking . On the e masks) , 48. Groe masks) . It was e masks) . However (dsDNA) . Under t (dsDNA) .3C2)-based structures to repair bone defects; MXene structures were incorporated into composite scaffolds constructed from hydroxyapatite and sodium alginate through extrusion-based 3D printing for bone regeneration. These scaffolds with uniform structures and macropore morphologies had significant mechanical strength with improved alkaline phosphatase performance, upregulated osteogenic gene expression, suitable biocompatibility, and stimulated mineralized-nodule generation/cell proliferation. They could efficiently promote the regeneration of bone (in vivo), providing great opportunities for bone healing [3C2) quantum dots with immunomodulatory effects have been explored for improving tissue repairing after injury. They selectively reduced the human CD4+IFN‐γ+ T‐lymphocytes activation and stimulated the expansion of immunosuppressive CD4+CD25+FoxP3+ regulatory T‐cells in a triggered lymphocyte population [Different types of MXene and graphene-based (nano)composites have been deployed for tissue engineering and regenerative medicine purposes, with efficient multifunctionality and good biocompatibility. Mi et al.  introduc healing . Notably healing . They ha healing . MXene -graphene hybrid films were synthesized using a mixing-drying technique to produce biosensors for glucose detection /graphene/polydimethylsiloxane layered structures fabricated via vacuum filtration and pre-polymerization mainly contained two layers of MXenes (upper layer) and flexible graphene/polydimethylsiloxane composites (bottom layer). These composite films could be deployed in designing wearable strain sensors  with a large range of linear response, as well as high sensitivity (low limit of detection was ~0.025%), linearity (R2 > 0.98), and cycling stability  [The designed MXene-graphene hybrids have been applied as flexible supercapacitors, electrodes, ion batteries, and EMI-shielding –58. Howe protein . Additio protein . In one ion Fig. . Consequ cycles) .Fig. 4A 3C2TX)-graphene oxide film-based sensors were designed with flexibility, conductivity, and cycling stability advantages [3C2Tx) composites. The designed temperature sensor exhibited high sensitivity/accuracy and competitive thermos-power output (~53.6 μV/°C) with great flexibility/stability (negligible degradations after 1000 bending cycles), opening many opportunities for manufacturing multifunctional devices with biomedical potentials [e.g., respiratory monitoring sensors) [−1 from 0–500 Pa, 126 kPa−1 from 500 Pa–7.5 kPa) and high conductivity were designed utilizing MXene-reduced graphene oxide aerogels [Layer-structured homogenous MXene (Tivantages . One stusensors) . Furtheraerogels . These saerogels .Graphene-based materials have been extensively used in various biomedical applications such as bioimaging, biosensing, theranostics, drug/gene delivery, antibacterials/antivirals, and tissue engineering applications. Therefore, for any effective and successful translation of these materials and becoming commercialized products, there should be a significant exposure of the human body to graphene-based materials, which makes it essential to evaluate the degree of biocompatibility and cytotoxicity of these materials to human cells. The potential cytotoxic effects of graphene-based materials on human cells mainly depend on their physicochemical characteristics, the nature of their interaction with cells, and their accumulation in specific tissues/organs . The tox3C2Tx) was analyzed for possible toxicity in a zebrafish embryo model (in vivo assessments) [−1, the lethal concentration 50 ≈257.46 μg mL−1, and LOEC (lowest observed effect concentration) ≈100 μg mL−1. Notably, no meaningful teratogenic influences could be detected in the examined model at 100 μg mL−1. After locomotion and neurotoxicity assessments, MXenes (50 μg mL−1) demonstrated no harmful influences on neuromuscular performances. Based on the results at concentrations below 100 μg mL−1, these MXene structures could be categorized as practically nontoxic based on the Acute Toxicity Rating Scale (ATRS) by the Fish and Wildlife Service [For clinical translation of MXene- and graphene-based (nano)structures, future studies should be comprehensively focused on (eco)toxicological and cytotoxicity properties of these materials –72. For ssments) . Accordi Service . By deve Service –78. Also Service . Another Service , 81.e.g., cellulose or chitosan nanofibers) can be combined with MXenes and graphene structures to improve their biomedical applicability. Additionally, the commercialization and eco-friendly manufacturing of these structures should be comprehensively explored to find inexpensive and up-scalable strategies with higher safety profile. Optimization of reaction conditions, environmental stability, surface chemistry characterizations, nanotoxicological studies, systematic biocompatibility analyses (both in vitro and in vivo), and pre-/clinical assessments still need to be addressed. MXene structures with single-layer, fewer defects, and larger size had higher conductivity, illustrating that the synthesis conditions and their properties can significantly affect their quality and future applications; the intrinsic features of MXenes and graphene can be improved by controlling reaction mixture conditions , surface functional groups/terminations, and interlayer spacing.MXene-graphene hybrids have been explored due to their fascinating physicochemical properties, which make them attractive candidates for future biomedical explorations. Although MXenes-graphene nanomaterials have attracted wide attention in bio- and nanomedicine, their possible applications for drug delivery, cancer therapy, and theranostics are still uncertain concerning their biocompatibility and toxicity, lack of clinical assessments, and enough specificity/selectivity. Their biological sensing and imaging properties are typically restricted by their non-specific adsorption. MXenes with a larger interlayer spacing had higher specific surface area and additional exposed active sites. In this context, hybridization or surface modifications can remarkably improve multifunctionality and reduce the possible toxicity of these structures. Natural polymers (


The graphene–silicon junction is one of the simplestconceivableinterfaces in graphene-integrated semiconductor technology that canlead to the development of future generation of electronic and optoelectronicdevices. However, graphene’s integration is currently expensiveand time-consuming and shows several challenges in terms of large-scaledevice fabrication, effectively preventing the possibility of implementingthis technology into industrial processes. Here, we show a simpleand cost-effective fabrication technique, based on inkjet printing,for the realization of printed graphene–silicon rectifyingdevices. The printed graphene–silicon diodes show an ON/OFFratio higher than 3 orders of magnitude and a significant photovoltaiceffect, resulting in a fill factor of ∼40% and a photocurrentefficiency of ∼2%, making the devices suitable for both electronicand optoelectronic applications. Finally, we demonstrate large-areapixeled photodetectors and compatibility with back-end-of-line fabricationprocesses. However,the future generation of electronic devices does require the use ofthinner materials with higher electronic performance, which cannotbe achieved with traditional semiconducting bulk materials.4 In addition to the unique propertiesof these materials, their dimensionality and low-temperature integrationenable easy integration in a standard Si CMOS process flow.4 Indeed, back-end-of-line (BEOL) process techniques,where graphene is used as last layer of the process, have been usedto demonstrate graphene–Si prototypes, such as graphene gassensors,5 optical receivers,6 and image sensor arrays.7The family of two-dimensional (2D) materials,in particular, graphene,represents a very attractive platform for the future generation ofelectronics and optoelectronics.8 For this reason, in the past few years, severalstudies have reported the fabrication of graphene–silicon-basedrectifying or barrier-variable devices,10 photovoltaiccells,11 bias-tunable photodetectors,13 chemical sensors,14 and Schottky-barrier-basedfield-effect transistors.15 Despite thesepromising results, there are still several challenges associated withoptimizing the material integration and device performance.4 In particular, previous works did focus on graphene produced bychemical vapor deposition (CVD), whose integration into a siliconchip requires to finely control the material growth (grain-free graphenewill provide better performance) and to minimize wrinkle formationand residue associated with the transfer process,17 hence enabling device reproducibility. These challenges not onlymake the integration process expensive in terms of time and money,but it also considerably limits the possibility of extending the fabricationprocess on a large scale, effectively preventing the possibility ofimplementing this technology in an industrial process.The graphene–silicon junction is one of the simplestconceivabledevices in a graphene-integrated semiconductor technology. Not onlydoes it offers a great opportunity to study the physics occurringat the interface between a 2D and a 3D material, but it also providesthe possibility to realize electronic devices with outstanding properties.18 It also enables reductionof materials and energy consumption, limiting the number of processingsteps and the waste production during the fabrication.18 Graphene and 2D materials can be easily formulatedin inkjet printable inks, either by using liquid phase exfoliation(LPE)20 or electrochemical exfoliation.21 Many works have reported hybrid or fully printedelectronic devices made of 2D materials,26 but to date, a printed graphene–silicon diode has never beenreported in the literature.In thisframework, inkjet printing represents a very attractivetechnique for device fabrication because of its scalability and costeffectiveness.2 from the silicon substrate. Then grapheneis inkjet-printed on the exposed area to allow the formation of thegraphene–silicon junction. The obtained devices show a typicaldiode behavior with an ON/OFF ratio (measured in air and at room temperature)of about 3 orders of magnitude. Several theoretical models have beenapplied to study the transport mechanisms of the junction and to estimatethe figures of merit of the diode, such as the Schottky barrier heightand the ideality factor. Furthermore, the behavior of the devicesat different temperatures and under light irradiation is investigated.A significant photovoltaic effect is observed, making the diode suitablefor advanced optoelectronic applications, such as photodetectors ableto work in the long-wavelength range. In this framework, we demonstratea device made of a network of printed diodes made on the same substrate,which acts as a spatially selective photodetector; i.e., the deviceallows one to identify which area of the chip has been irradiatedwith white light through the measurement of the variation of currentmeasured by different diodes. Finally, to demonstrate the ease oflarge-scale production through this technique and compatibility withSi technology in a BEOL process, we fabricated the same diode on aprepatterned silicon substrate, where the oxide layers were selectivelyremoved with standard clean-room-based etching techniques.In this work, we present a simpleand cost-effective fabricationtechnique for the realization of printed graphene–silicon rectifyingdevices. Mechanical scratching is used to remove a small region ofthermally grown SiOInconclusion, we demonstrate that inkjet printing offers a simpleway to integrate graphene into silicon-based electronics, which canbe used to fabricate diodes with a high ON/OFF ratio and a strongphotovoltaic response that make them suitable for optoelectronic applications.2  of ∼103 at V = ±2 V. The polarity of the diodeis consistent with the formation of a n–n heterojunction betweenthe slightly doped graphene27 and n-typesilicon.28 Measurements have been performedon 12 samples, showing reproducible results. The I–V characteristics of all of the devicestested are reported in section II in the Supporting Information. Note that no rectifying behavior was observedwhen graphene was replaced by metallic electrodes (section II of the Supporting Information).Devices wereprepared on doped n-Si (100) wafers covered with 300 nm thermallygrown SiO2 see . An area surface 1A. A wat surface  and was 28I0 is thereverse saturation current, q is the electron charge, n is the ideality factor, k is the Boltzmannconstant, and T is the temperature. In the case ofpure thermionic transport, n should be 1, but interfacialdefects as well as unwanted insulating layers can lead to Schottkybarrier inhomogeneities increasing the ideality factor.30 The fit of V = −0.2 V. This is expectedsince in this range any series resistance can be neglected. The bestfit is obtained with I0 = −1.4× 10–10 A and n = 2.1. Accordingto the thermionic emission theory, the reverse saturation currentcan be written as:28S is the area of thejunction, A* is the Richardson constant (112 cm–2 K–2 for n-Si31), and φb0 is the Schottky barrierat zero voltage. By using I0 = −1.4× 10–10 A, we obtain φb0 = 0.89 eV. This value seems too high and is likely overestimateddue to the arbitrary choice of the fitting region and the A* value that can be quite different from the theoreticalone in real devices. To improve the fit, we consider a more realisticmodel that takes into account the possible presence of a series resistance Rs, which describes the diode current with thefollowing equation:3233 to obtain the diode parameters: for V – RsI ≫ nkT/q, Rs and n. Then defining thefollowing function:33Supporting Information, we obtain Rs = 35 kΩ, n = 2.7, and φb0 = 0.28. The blue dashed curve in V – RsI ≃ 0, where the diode equation . This discrepancy islikely due both to graphene being doped (n-doping would raise theFermi level reducing its work function) and to a probable Fermi levelpinning caused by the presence of defects or impurities at the junctioninterface, in agreement with what was observed in other works basedon CVD graphene.38To furtherinvestigate the conduction mechanisms of the diode,we study how the current in the devices is affected by the temperature. I–V characteristicsat different temperatures have been used to construct the Richardson’splot and to estimate the values of A* and φb0 through a different method . Although the originof a lower effective Richardson constant has been attributed to differentphenomena, such as the massless Dirac fermion nature of carriers ingraphene,39 a Landauer transport mechanism40 or the presence of a native oxide layer at theGr–Si interface,30 it can be seenthe A* and φb0 obtainedthrough Richardson’s method are very unrealistic as they areaveraged on I–V curves inwhich the thermionic emission is not the only conduction mechanism,such as those at low temperatures. Hence, we can state that Cheung’smethod gives a better estimate of the diode parameters among the modelsused.The I–V characteristics of the Gr–Si diodein the dark and under illumination by a supercontinuum white laser.The measurement carried out under light exposure shows that the I–V curve is shifted to the left,compared to the one obtained under dark conditions, indicating anevident photovoltaic effect. When the Gr–Si junction is irradiatedby light, the Si substrate absorbs photons with energy higher thanthe band gap, and electron–hole pairs are generated. Thesepairs are quickly separated by the built-in field of the Gr–Sijunction formed in the depletion zone, and electrons and holes arecollected at the electrodes, generating the observed photocurrent.Moreover, electrons from graphene can also be excited over the Schottkybarrier and contribute to the photocurrent.13 The parameters commonly used to evaluate the performance of a photovoltaicdevice are the open-circuit voltage (Voc), the short-circuit current (Isc), thefill factor (FF), and the power conversion efficiency (PCE). Voc corresponds to the maximum voltage availablefrom the photovoltaic device, and it occurs when the current is zero.It matches the amount of direct polarization on the junction due tothe illumination, and it has a logarithmic dependence on the intensityof light. In our case, we obtain Voc ∼0.2 V, comparable to values reported from graphene–siliconheterojunction-based devices.42Isc is the current measured when the voltage across the deviceis zero. It is entirely due to generation and collection of carriersgenerated by the light, and it corresponds to the maximum currentachievable by the photovoltaic device. We observe a significant currentof a few nA, confirming the good photovoltaic performance of our diodes.FF is defined as the ratio between the maximum power of the device(Imax·Vmax) and that of the one of the ideal device (FF = (Imax·Vmax)/(Isc·Voc)), and in ourcase, it results in FF ∼ 40%. PCE is defined as the ratio betweenthe energy output from the device and the intensity of the incidentlight (Imax·Vmax/Plight). Despite being stronglyinfluenced by several factors, such as the intensity of light andthe temperature of the device, the PCE is the most commonly used parameterto compare the performance of different photovoltaic devices. In ourcase, we obtain a PCE of ∼2%, which is a good achievement comparedto values commonly reported in the literature for CVD graphene withno further processing (see section III in the Supporting Information), considering the low intensity ofthe incident light and that our devices have not been subjected toany engineering process.43 In particular, ourresults indicate that Si–Gr devices with good performance canbe achieved using printed graphene films; i.e., parameters such assheet resistance and mobility have little effect on the device performance,as also theoretically shown in ref /Idark) calculated at V = 2 V, as shown in in section III in the Supporting Information, follows a linear relationship which ensures thata maximum light effect is reached at the maximum laser power. Therefore,we further investigated the optical response of the devices settinga power of 100 μW/cm2 to test the Gr–Si devicein photocurrent and photovoltage modes. V =0 V and I = 0 A, respectively. It is observed that,under illumination, the device generates both a current and a voltage;i.e., it can be operated in a self-powered mode for over 15 min ofcontinuous cycles. Dark–light–dark sequences have beenused to estimate the characteristic time for the electron–holepairs’ photoexcitation and recombination, respectively. In Supporting Information section III, we show thatthe electron–hole couple generation and recombination timeare 0.38 and 0.25 s, respectively.I–V characteristics of the fourdiodes simultaneously measured under dark conditions: all four diodesshow the same electrical behavior, with slightly different currentvalues mainly due to different series resistances. To test the deviceas a photodetector, the current in the four diodes was measured whilesetting a common bias of V = 0 V on all devices andalternating 20 s in the dark and 20 s of light irradiation only ondiode 1. 45 so the least resistive pathfor the holes is the one through the graphene and not the one throughthe substrate. This conduction mechanism is confirmed when testingthe photodetector using only two or three diodes, as shown in sectionIII of the Supporting Information. Theobserved feature allows the photodetector to be used in self-poweredmode. Indeed, it is possible to identify the irradiated area of thechip simply by looking at the current sign. Furthermore, by illuminatinga single junction, it is possible to generate current in all of theother diodes, considerably improving the photovoltaic efficiency ofthe device as a consequence of an improved charge collection. Theresolution of our detector is in the range of few millimeters  but is limited by the size of thelaser spot. Indeed, the resolution of the photodetector could easilybe further improved by using a focused laser beam.The potential of the “scratchand print” approachproposed in this work enables a network of diodes to be made in avery simple and fast way. To demonstrate this idea, we realized adevice with four parallel diodes . Doped n-Si (100) wafers with a resistivityof ∼10 Ω·cm, corresponding to a phosphorus dopantdensity of ∼4.5 × 1046 Note that the nanosheets are exfoliated withnoncovalent functionalization in water, so the thickness of the nanosheetalso includes a contribution from the stabilizer molecules adsorbedon both sides of the flake.46 Previouscharacterization shows that the nanosheets have high crystallinity,and they are C–O free.47 A VarianCary 5000 UV–vis spectrometer was used to measure the absorptionspectrum of the ink. The Lambert–Beer law was used to obtainthe concentration of graphene by using an absorption coefficient of2460 measured at 660 nm.48 Immediatelybefore printing, the Si substrates were cleaned with acetone, isopropylalcohol, and DI water. A Dimatix Materials Printer 2850 (Fujifilm)was used to print 2 mg mL–1 graphene ink on topof the scratched area. The spatial resolution of the printer is ∼50μm on silicon. The platen temperature was set at 42 °C,and cartridges with a droplet volume of 10 pL were used, setting adrop spacing of 35 μm and 80 printing passes.The water-based inks wereprepared as described in ref . The graSupporting Information). Electrical measurements were performed with aJanis probe station (Janis ST-500 probe station) equipped with fournanoprobes connected to a Keithley 4200 SCS (semiconductor characterizationsystem), working as source-measurement unit with current sensitivitybetter than 1 pA. The electrical measurements were performed in apressure range from 1 bar (room pressure) to 10–5 mbar, obtained by evacuating the air in the chamber by a rough anda turbo pump, and at different temperatures from 220 to 400 K. Thephotoconductivity was tested by irradiating the devices with a supercontinuouswhite laser source .A Bruker Dektak XT system wasused to measure the roughness of the substrate and the thickness ofthe printed graphene (section I in the